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Entry
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- *109135 - AXL RECEPTOR TYROSINE KINASE; AXL
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- OMIM
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<p>
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<span class="h4">*109135</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div id="mimFloatingLinksMenu">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000167601;t=ENST00000301178" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=558" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=109135" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000167601;t=ENST00000301178" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001278599,NM_001699,NM_021913" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_021913" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=109135" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=00171&isoform_id=00171_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/AXL" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/37593,37595,238775,292870,21536466,21536468,21619004,119577426,119577427,311362127,311362129,520260399,1375383940,2515420489,2515420491,2515420493,2515420495" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/P30530" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=558" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000167601;t=ENST00000301178" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=AXL" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=AXL" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+558" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/AXL" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:558" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/558" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr19&hgg_gene=ENST00000301178.9&hgg_start=41219223&hgg_end=41261766&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=109135[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=109135[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/AXL/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000167601" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=AXL" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=AXL" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=AXL&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA25197" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:905" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1347244" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/AXL#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:1347244" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/558/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=558" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-100812-8" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:558" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=AXL&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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109135
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</span>
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</span>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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AXL RECEPTOR TYROSINE KINASE; AXL
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</span>
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</h3>
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</div>
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<div>
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<br />
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<div>
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<h4>
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<span class="mim-font">
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ONCOGENE AXL<br />
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AXL TRANSFORMING GENE
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</h4>
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</div>
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<div>
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<br />
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=AXL" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">AXL</a></em></strong>
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</span>
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</p>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/19/724?start=-3&limit=10&highlight=724">19q13.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr19:41219223-41261766&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">19:41,219,223-41,261,766</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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<div>
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<br />
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div>
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<a id="cloning" class="mim-anchor"></a>
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<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</h4>
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<div id="mimCloningFold" class="collapse in mimTextToggleFold">
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<span class="mim-text-font">
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<p>In an effort to determine genes involved in the progression of chronic myelogenous leukemia (CML; <a href="/entry/608232">608232</a>) to acute-phase leukemia, <a href="#4" class="mim-tip-reference" title="Liu, E., Hjelle, B., Bishop, J. M. <strong>Transforming genes in chronic myelogenous leukemia.</strong> Proc. Nat. Acad. Sci. 85: 1952-1956, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3279421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3279421</a>] [<a href="https://doi.org/10.1073/pnas.85.6.1952" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3279421">Liu et al. (1988)</a> identified a transforming gene in the DNAs of 2 patients with this disorder. <a href="#9" class="mim-tip-reference" title="O'Bryan, J. P., Frye, R. A., Cogswell, P. C., Neubauer, A., Kitch, B., Prokop, C., Espinosa, R., III, Le Beau, M. M., Earp, H. S., Liu, E. T. <strong>Axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase.</strong> Molec. Cell. Biol. 11: 5016-5031, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1656220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1656220</a>] [<a href="https://doi.org/10.1128/mcb.11.10.5016-5031.1991" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1656220">O'Bryan et al. (1991)</a> found by molecular cloning and characterization of this gene, which they termed AXL (from the Greek word 'anexelekto,' or uncontrolled), that it is a receptor tyrosine kinase with a structure novel among tyrosine kinases. They showed that the AXL protein is capable of transforming NIH 3T3 cells. Furthermore, its transforming capacity results from overexpression of AXL mRNA rather than from structural mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1656220+3279421" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Janssen, J. W. G., Schulz, A. S., Steenvoorden, A. C. M., Schmidberger, M., Strehl, S., Ambros, P. F., Bartram, C. R. <strong>A novel putative tyrosine kinase receptor with oncogenic potential.</strong> Oncogene 6: 2113-2120, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1834974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1834974</a>]" pmid="1834974">Janssen et al. (1991)</a> independently found transforming activity by a tumorigenicity assay using NIH 3T3 cells transfected with DNA from a patient with a chronic myeloproliferative disorder. They reported the cDNA cloning of the corresponding oncogene, which they designated UFO, in allusion to the unidentified function of the protein. Nucleotide sequence analysis revealed a 2,682-bp open reading frame capable of directing the synthesis of an 894-amino acid polypeptide. It was evolutionarily conserved among vertebrate species. The predicted protein showed features characteristic of a transmembrane receptor with tyrosine kinase activity. The gene was transcribed into two 5.0-kb and 3.2-kb mRNAs in human bone marrow and human tumor cell lines. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1834974" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
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<br />
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<div>
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<a id="geneFunction" class="mim-anchor"></a>
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<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</h4>
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<span class="mim-text-font">
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<p>The transforming activity of AXL demonstrates that the receptor can drive cellular proliferation. Although the function of AXL in nontransformed cells and tissues was unknown, <a href="#13" class="mim-tip-reference" title="Varnum, B. C., Young, C., Elliott, G., Garcia, A., Bartley, T. D., Fridell, Y.-W., Hunt, R. W., Trail, G., Clogston, C., Toso, R. J., Yanagihara, D., Bennett, L., Sylber, M., Merewether, L. A., Tseng, A., Escobar, E., Liu, E. T., Yamane, H. K. <strong>Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6.</strong> Nature 373: 623-626, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7854420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7854420</a>] [<a href="https://doi.org/10.1038/373623a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7854420">Varnum et al. (1995)</a> suspected that it may involve the stimulation of cell proliferation in response to an appropriate signal, i.e., a ligand that activates the receptor. <a href="#13" class="mim-tip-reference" title="Varnum, B. C., Young, C., Elliott, G., Garcia, A., Bartley, T. D., Fridell, Y.-W., Hunt, R. W., Trail, G., Clogston, C., Toso, R. J., Yanagihara, D., Bennett, L., Sylber, M., Merewether, L. A., Tseng, A., Escobar, E., Liu, E. T., Yamane, H. K. <strong>Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6.</strong> Nature 373: 623-626, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7854420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7854420</a>] [<a href="https://doi.org/10.1038/373623a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7854420">Varnum et al. (1995)</a> purified an AXL stimulatory factor and identified it as the product of the growth arrest-specific gene-6 (GAS6; <a href="/entry/600441">600441</a>) (<a href="#7" class="mim-tip-reference" title="Manfioletti, G., Brancolini, C., Avanzi, G., Schneider, C. <strong>The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade.</strong> Molec. Cell. Biol. 13: 4976-4985, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8336730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8336730</a>] [<a href="https://doi.org/10.1128/mcb.13.8.4976-4985.1993" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8336730">Manfioletti et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8336730+7854420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Loss of function of the 3 TAM receptors, Tyro3 (<a href="/entry/600341">600341</a>), Axl, and Mer (MERTK; <a href="/entry/604705">604705</a>), results in profound dysregulation of the immune response in mice (see ANIMAL MODEL). By analyzing TAM function in the dendritic cell subset of mouse antigen-presenting cells, <a href="#11" class="mim-tip-reference" title="Rothlin, C. V., Ghosh, S., Zuniga, E. I., Oldstone, M. B. A., Lemke, G. <strong>TAM receptors are pleiotropic inhibitors of the innate immune response.</strong> Cell 131: 1124-1136, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18083102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18083102</a>] [<a href="https://doi.org/10.1016/j.cell.2007.10.034" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18083102">Rothlin et al. (2007)</a> found that TAM inhibited inflammation through an essential stimulator of inflammation, Ifnar (<a href="/entry/107450">107450</a>), and its associated transcription factor, Stat1 (<a href="/entry/600555">600555</a>). Toll-like receptor (TLR; see <a href="/entry/601194">601194</a>) induction of Ifnar-Stat1 signaling upregulated the TAM system, which, in turn, induced the cytokine and TLR suppressors Socs1 (<a href="/entry/603597">603597</a>) and Socs3 (<a href="/entry/604176">604176</a>). <a href="#11" class="mim-tip-reference" title="Rothlin, C. V., Ghosh, S., Zuniga, E. I., Oldstone, M. B. A., Lemke, G. <strong>TAM receptors are pleiotropic inhibitors of the innate immune response.</strong> Cell 131: 1124-1136, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18083102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18083102</a>] [<a href="https://doi.org/10.1016/j.cell.2007.10.034" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18083102">Rothlin et al. (2007)</a> concluded that cytokine-dependent activation of TAM signaling diverts a proinflammatory pathway to provide an intrinsic feedback inhibitor of both TLR- and cytokine-driven immune responses. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18083102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Pseudotypes are viral particles that carry the genome of one virus and 1 or more proteins of another virus (<a href="#12" class="mim-tip-reference" title="Temperton, N. J., Wright, E. <strong>Retroviral pseudotypes. In: Encyclopedia of Life Sciences.</strong> Chichester, England: John Wiley & Sons, Ltd. 2009."None>Temperton and Wright, 2009</a>). <a href="#8" class="mim-tip-reference" title="Morizono, K., Xie, Y., Olafsen, T., Lee, B., Dasgupta, A., Wu, A. M., Chen, I. S. Y. <strong>The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry.</strong> Cell Host Microbe 9: 286-298, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21501828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21501828</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21501828[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.chom.2011.03.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21501828">Morizono et al. (2011)</a> studied the infectivity of lentivirus pseudotypes lacking envelope binding and observed residual high infectivity for some cell types. The retained infectivity was conferred by soluble bovine protein S in the culture medium. <a href="#8" class="mim-tip-reference" title="Morizono, K., Xie, Y., Olafsen, T., Lee, B., Dasgupta, A., Wu, A. M., Chen, I. S. Y. <strong>The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry.</strong> Cell Host Microbe 9: 286-298, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21501828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21501828</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21501828[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.chom.2011.03.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21501828">Morizono et al. (2011)</a> showed that bovine protein S and its human homolog, GAS6, mediated binding of the virus to target cells by bridging virion envelope phosphatidylserine to AXL present on target cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21501828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Paolino, M., Choidas, A., Wallner, S., Pranjic, B. Uribesalgo, I., Loeser, S., Jamieson, A. M., Langdon, W. Y., Ikeda, F., Fededa, J. P., Cronin, S. J., Nitsch, R., and 12 others. <strong>The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells.</strong> Nature 507: 508-512, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24553136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24553136</a>] [<a href="https://doi.org/10.1038/nature12998" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24553136">Paolino et al. (2014)</a> demonstrated that genetic deletion of the E3 ubiquitin ligase CBLB (<a href="/entry/604491">604491</a>) or targeted inactivation of its E3 ligase activity licenses natural killer (NK) cells to spontaneously reject metastatic tumors. The TAM tyrosine kinase receptors TYRO3, AXL, and MERTK were identified as ubiquitylation substrates for CBLB. Treatment of wildtype NK cells with a small molecule TAM kinase inhibitor conferred therapeutic potential, efficiently enhancing antimetastatic NK cell activity in vivo. Oral or intraperitoneal administration using this TAM inhibitor markedly reduced murine mammary cancer and melanoma metastases dependent on NK cells. <a href="#10" class="mim-tip-reference" title="Paolino, M., Choidas, A., Wallner, S., Pranjic, B. Uribesalgo, I., Loeser, S., Jamieson, A. M., Langdon, W. Y., Ikeda, F., Fededa, J. P., Cronin, S. J., Nitsch, R., and 12 others. <strong>The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells.</strong> Nature 507: 508-512, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24553136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24553136</a>] [<a href="https://doi.org/10.1038/nature12998" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24553136">Paolino et al. (2014)</a> further reported that the anticoagulant warfarin exerts antimetastatic activity in mice via Cblb/TAM receptors in NK cells, providing a molecular explanation for the effect of warfarin to reduce tumor metastases in rodent models. <a href="#10" class="mim-tip-reference" title="Paolino, M., Choidas, A., Wallner, S., Pranjic, B. Uribesalgo, I., Loeser, S., Jamieson, A. M., Langdon, W. Y., Ikeda, F., Fededa, J. P., Cronin, S. J., Nitsch, R., and 12 others. <strong>The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells.</strong> Nature 507: 508-512, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24553136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24553136</a>] [<a href="https://doi.org/10.1038/nature12998" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24553136">Paolino et al. (2014)</a> concluded that this novel TAM/CBLB inhibitory pathway shows that it might be possible to develop a 'pill' that awakens the innate immune system to kill cancer metastases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24553136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Fourgeaud, L., Traves, P. G., Tufail, Y., Leal-Bailey, H., Lew, E. D., Burrola, P. G., Callaway, P., Zagorska, A., Rothlin, C. V., Nimmerjahn, A., Lemke, G. <strong>TAM receptors regulate multiple features of microglial physiology.</strong> Nature 532: 240-244, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27049947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27049947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27049947[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature17630" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27049947">Fourgeaud et al. (2016)</a> demonstrated that the TAM receptor tyrosine kinases Mer and Axl regulate the microglial functions of damage sensing and routine noninflammatory clearance of dead brain cells. <a href="#2" class="mim-tip-reference" title="Fourgeaud, L., Traves, P. G., Tufail, Y., Leal-Bailey, H., Lew, E. D., Burrola, P. G., Callaway, P., Zagorska, A., Rothlin, C. V., Nimmerjahn, A., Lemke, G. <strong>TAM receptors regulate multiple features of microglial physiology.</strong> Nature 532: 240-244, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27049947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27049947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27049947[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature17630" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27049947">Fourgeaud et al. (2016)</a> found that adult mice deficient in microglial Mer and Axl exhibit a marked accumulation of apoptotic cells specifically in neurogenic regions of the central nervous system (CNS), and that microglial phagocytosis of the apoptotic cells generated during adult neurogenesis is normally driven by both TAM receptor ligands Gas6 and protein S (<a href="/entry/176880">176880</a>). Using live 2-photon imaging, the authors demonstrated that the microglial response to brain damage is also TAM-regulated, as TAM-deficient microglia display reduced process motility and delayed convergence to sites of injury. <a href="#2" class="mim-tip-reference" title="Fourgeaud, L., Traves, P. G., Tufail, Y., Leal-Bailey, H., Lew, E. D., Burrola, P. G., Callaway, P., Zagorska, A., Rothlin, C. V., Nimmerjahn, A., Lemke, G. <strong>TAM receptors regulate multiple features of microglial physiology.</strong> Nature 532: 240-244, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27049947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27049947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27049947[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature17630" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27049947">Fourgeaud et al. (2016)</a> also showed that microglial expression of Axl is prominently upregulated in the inflammatory environment that develops in a mouse model of Parkinson disease (<a href="/entry/168600">168600</a>). <a href="#2" class="mim-tip-reference" title="Fourgeaud, L., Traves, P. G., Tufail, Y., Leal-Bailey, H., Lew, E. D., Burrola, P. G., Callaway, P., Zagorska, A., Rothlin, C. V., Nimmerjahn, A., Lemke, G. <strong>TAM receptors regulate multiple features of microglial physiology.</strong> Nature 532: 240-244, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27049947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27049947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27049947[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature17630" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27049947">Fourgeaud et al. (2016)</a> concluded that these results established TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27049947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using single-cell RNA sequencing in human and mouse non-small-cell lung cancers, <a href="#6" class="mim-tip-reference" title="Maier, B., Leader, A. M., Chen, S. T., Tung, N., Chang, C., LeBerichel, J., Chudnovskiy, A., Maskey, S., Walker, L., Finnigan, J. P., Kirkling, M. E., Reizis, B., and 11 others. <strong>A conserved dendritic-cell regulatory program limits antitumour immunity.</strong> Nature 580: 257-262, 2020. Note: Erratum: Nature 582: E17, 2020. Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32269339/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32269339</a>] [<a href="https://doi.org/10.1038/s41586-020-2134-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32269339">Maier et al. (2020)</a> identified a cluster of dendritic cells (DCs) that they named 'mature dendritic cells enriched in immunoregulatory molecules' (mregDCs), owing to their coexpression of immunoregulatory genes and maturation genes. <a href="#6" class="mim-tip-reference" title="Maier, B., Leader, A. M., Chen, S. T., Tung, N., Chang, C., LeBerichel, J., Chudnovskiy, A., Maskey, S., Walker, L., Finnigan, J. P., Kirkling, M. E., Reizis, B., and 11 others. <strong>A conserved dendritic-cell regulatory program limits antitumour immunity.</strong> Nature 580: 257-262, 2020. Note: Erratum: Nature 582: E17, 2020. Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32269339/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32269339</a>] [<a href="https://doi.org/10.1038/s41586-020-2134-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32269339">Maier et al. (2020)</a> found that the mregDC program is expressed by canonical DC1s and DC2s upon uptake of tumor antigens and further found that upregulation of PDL1 (<a href="/entry/605402">605402</a>), a key checkpoint molecule, in mregDCs is induced by the receptor tyrosine kinase AXL, while upregulation of interleukin-12 (IL12; see <a href="/entry/161560">161560</a>) depends strictly on interferon-gamma (IFNG; <a href="/entry/147570">147570</a>) and is controlled negatively by IL4 (<a href="/entry/147780">147780</a>) signaling. Blocking IL4 enhances IL12 production by tumor antigen-bearing mregDC1s, expands the pool of tumor-infiltrating effector T cells, and reduces tumor burden. <a href="#6" class="mim-tip-reference" title="Maier, B., Leader, A. M., Chen, S. T., Tung, N., Chang, C., LeBerichel, J., Chudnovskiy, A., Maskey, S., Walker, L., Finnigan, J. P., Kirkling, M. E., Reizis, B., and 11 others. <strong>A conserved dendritic-cell regulatory program limits antitumour immunity.</strong> Nature 580: 257-262, 2020. Note: Erratum: Nature 582: E17, 2020. Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32269339/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32269339</a>] [<a href="https://doi.org/10.1038/s41586-020-2134-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32269339">Maier et al. (2020)</a> concluded that they uncovered a regulatory module associated with tumor-antigen uptake that reduces DC1 functionality in human and mouse cancers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32269339" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By fluorescence in situ hybridization, <a href="#9" class="mim-tip-reference" title="O'Bryan, J. P., Frye, R. A., Cogswell, P. C., Neubauer, A., Kitch, B., Prokop, C., Espinosa, R., III, Le Beau, M. M., Earp, H. S., Liu, E. T. <strong>Axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase.</strong> Molec. Cell. Biol. 11: 5016-5031, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1656220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1656220</a>] [<a href="https://doi.org/10.1128/mcb.11.10.5016-5031.1991" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1656220">O'Bryan et al. (1991)</a> localized the AXL gene to 19q13.2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1656220" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By nonisotopic in situ hybridization, <a href="#3" class="mim-tip-reference" title="Janssen, J. W. G., Schulz, A. S., Steenvoorden, A. C. M., Schmidberger, M., Strehl, S., Ambros, P. F., Bartram, C. R. <strong>A novel putative tyrosine kinase receptor with oncogenic potential.</strong> Oncogene 6: 2113-2120, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1834974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1834974</a>]" pmid="1834974">Janssen et al. (1991)</a> mapped the AXL gene to 19q13.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1834974" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#14" class="mim-tip-reference" title="Zhang, Z., Lee, J. C., Lin, L., Olivas, V., Au, V., LaFramboise, T., Abdel-Rahman, M., Wang, X., Levine, A. D., Rho, J. K., Choi, Y. J., Choi, C.-M., and 18 others. <strong>Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer.</strong> Nature Genet. 44: 852-860, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22751098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22751098</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22751098[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22751098">Zhang et al. (2012)</a> reported increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR (<a href="/entry/131550">131550</a>)-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR T790M alteration (<a href="/entry/131550#0006">131550.0006</a>) or MET activation. Genetic or pharmacologic inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 (<a href="/entry/600441">600441</a>) was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to tyrosine kinase inhibitors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22751098" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Regulation of lymphocyte numbers is mediated by cytokines signaling through receptors coupled to cytoplasmic protein-tyrosine kinases. <a href="#5" class="mim-tip-reference" title="Lu, Q., Lemke, G. <strong>Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family.</strong> Science 293: 306-311, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11452127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11452127</a>] [<a href="https://doi.org/10.1126/science.1061663" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11452127">Lu and Lemke (2001)</a> generated mice deficient in Mertk (<a href="/entry/604705">604705</a>), Axl, and Tyro3 (<a href="/entry/600341">600341</a>). Like their ligands, GAS6 and PROS1 (<a href="/entry/176880">176880</a>), these receptors are widely expressed in monocytes and macrophages but not in B or T lymphocytes. Although the peripheral lymphoid organs of mutant mice were indistinguishable from those of wildtype mice at birth, by 4 weeks of age spleens and lymph nodes grew at elevated rates. This was primarily due to the hyperproliferation of constitutively activated B and T cells, particularly CD4-positive T cells, with ectopic colonies in every adult organ examined. All triple mutants developed autoimmunity with symptoms histologically similar to human rheumatoid arthritis (<a href="/entry/180300">180300</a>), pemphigus vulgaris (<a href="/entry/169610">169610</a>), and systemic lupus erythematosus (<a href="/entry/152700">152700</a>), and were characterized by antibodies against normal cellular antigens, including phospholipids and double-stranded DNA. Females were particularly prone to thromboses and recurrent fetal loss. Flow cytometric analysis demonstrated that wildtype B and T cells underwent multiple rounds of cell division after injection into mutant mice and that their antigen-presenting cells expressed elevated levels of activation markers. <a href="#5" class="mim-tip-reference" title="Lu, Q., Lemke, G. <strong>Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family.</strong> Science 293: 306-311, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11452127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11452127</a>] [<a href="https://doi.org/10.1126/science.1061663" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11452127">Lu and Lemke (2001)</a> proposed that the cells that initiate lymphoproliferation and autoimmunity in the Tyro3 family mutants were the macrophages and dendritic cells that normally express the 3 receptor genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11452127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Angelillo-Scherrer, A., Burnier, L., Flores, N., Savi, P., DeMol, M., Schaeffer, P., Herbert, J.-M., Lemke, G., Goff, S. P., Matsushima, G. K., Earp, H. S., Vesin, C., Hoylaerts, M. F., Plaisance, S., Collen, D., Conway, E. M., Wehrle-Haller, B., Carmeliet, P. <strong>Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy.</strong> J. Clin. Invest. 115: 237-246, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15650770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15650770</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15650770[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI22079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15650770">Angelillo-Scherrer et al. (2005)</a> generated mice lacking 1 of the 3 Gas6 receptors: Tyro3, Axl, or Mertk. Loss of any 1 of the Gas6 receptors or delivery of a soluble extracellular domain of Axl that traps Gas6 protected the mice against life-threatening thrombosis. Loss of a Gas6 receptor did not prevent initial platelet aggregation but impaired subsequent stabilization of platelet aggregates, at least in part by reducing outside-in signaling and platelet granule secretion. Gas6, through its receptors, activated PI3K and Akt (see <a href="/entry/164730">164730</a>) and stimulated tyrosine phosphorylation of the beta-3 integrin (<a href="/entry/173470">173470</a>), thereby amplifying outside-in signaling via alpha-IIb (<a href="/entry/607759">607759</a>)-beta-3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15650770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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Angelillo-Scherrer, A., Burnier, L., Flores, N., Savi, P., DeMol, M., Schaeffer, P., Herbert, J.-M., Lemke, G., Goff, S. P., Matsushima, G. K., Earp, H. S., Vesin, C., Hoylaerts, M. F., Plaisance, S., Collen, D., Conway, E. M., Wehrle-Haller, B., Carmeliet, P.
|
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<strong>Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy.</strong>
|
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J. Clin. Invest. 115: 237-246, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15650770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15650770</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15650770[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15650770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI22079" target="_blank">Full Text</a>]
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Fourgeaud, L., Traves, P. G., Tufail, Y., Leal-Bailey, H., Lew, E. D., Burrola, P. G., Callaway, P., Zagorska, A., Rothlin, C. V., Nimmerjahn, A., Lemke, G.
|
|
<strong>TAM receptors regulate multiple features of microglial physiology.</strong>
|
|
Nature 532: 240-244, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27049947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27049947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27049947[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27049947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
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[<a href="https://doi.org/10.1038/nature17630" target="_blank">Full Text</a>]
|
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|
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</p>
|
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|
|
</li>
|
|
|
|
<li>
|
|
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|
|
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|
|
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|
|
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|
|
Janssen, J. W. G., Schulz, A. S., Steenvoorden, A. C. M., Schmidberger, M., Strehl, S., Ambros, P. F., Bartram, C. R.
|
|
<strong>A novel putative tyrosine kinase receptor with oncogenic potential.</strong>
|
|
Oncogene 6: 2113-2120, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1834974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1834974</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1834974" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
|
|
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|
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|
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|
|
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|
|
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|
|
Liu, E., Hjelle, B., Bishop, J. M.
|
|
<strong>Transforming genes in chronic myelogenous leukemia.</strong>
|
|
Proc. Nat. Acad. Sci. 85: 1952-1956, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3279421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3279421</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3279421" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
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[<a href="https://doi.org/10.1073/pnas.85.6.1952" target="_blank">Full Text</a>]
|
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Lu, Q., Lemke, G.
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<strong>Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family.</strong>
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Science 293: 306-311, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11452127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11452127</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11452127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1061663" target="_blank">Full Text</a>]
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Maier, B., Leader, A. M., Chen, S. T., Tung, N., Chang, C., LeBerichel, J., Chudnovskiy, A., Maskey, S., Walker, L., Finnigan, J. P., Kirkling, M. E., Reizis, B., and 11 others.
|
|
<strong>A conserved dendritic-cell regulatory program limits antitumour immunity.</strong>
|
|
Nature 580: 257-262, 2020. Note: Erratum: Nature 582: E17, 2020. Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32269339/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32269339</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32269339" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/s41586-020-2134-y" target="_blank">Full Text</a>]
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|
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|
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Manfioletti, G., Brancolini, C., Avanzi, G., Schneider, C.
|
|
<strong>The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade.</strong>
|
|
Molec. Cell. Biol. 13: 4976-4985, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8336730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8336730</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8336730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1128/mcb.13.8.4976-4985.1993" target="_blank">Full Text</a>]
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Morizono, K., Xie, Y., Olafsen, T., Lee, B., Dasgupta, A., Wu, A. M., Chen, I. S. Y.
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<strong>The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry.</strong>
|
|
Cell Host Microbe 9: 286-298, 2011.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21501828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21501828</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21501828[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21501828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.chom.2011.03.012" target="_blank">Full Text</a>]
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O'Bryan, J. P., Frye, R. A., Cogswell, P. C., Neubauer, A., Kitch, B., Prokop, C., Espinosa, R., III, Le Beau, M. M., Earp, H. S., Liu, E. T.
|
|
<strong>Axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase.</strong>
|
|
Molec. Cell. Biol. 11: 5016-5031, 1991.
|
|
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|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1656220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1656220</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1656220" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1128/mcb.11.10.5016-5031.1991" target="_blank">Full Text</a>]
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Paolino, M., Choidas, A., Wallner, S., Pranjic, B. Uribesalgo, I., Loeser, S., Jamieson, A. M., Langdon, W. Y., Ikeda, F., Fededa, J. P., Cronin, S. J., Nitsch, R., and 12 others.
|
|
<strong>The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells.</strong>
|
|
Nature 507: 508-512, 2014.
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24553136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24553136</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24553136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature12998" target="_blank">Full Text</a>]
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<a id="Rothlin2007" class="mim-anchor"></a>
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<div class="">
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Rothlin, C. V., Ghosh, S., Zuniga, E. I., Oldstone, M. B. A., Lemke, G.
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<strong>TAM receptors are pleiotropic inhibitors of the innate immune response.</strong>
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Cell 131: 1124-1136, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18083102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18083102</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18083102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.cell.2007.10.034" target="_blank">Full Text</a>]
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Temperton, N. J., Wright, E.
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<strong>Retroviral pseudotypes. In: Encyclopedia of Life Sciences.</strong>
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Chichester, England: John Wiley & Sons, Ltd. 2009.
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<a id="Varnum1995" class="mim-anchor"></a>
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Varnum, B. C., Young, C., Elliott, G., Garcia, A., Bartley, T. D., Fridell, Y.-W., Hunt, R. W., Trail, G., Clogston, C., Toso, R. J., Yanagihara, D., Bennett, L., Sylber, M., Merewether, L. A., Tseng, A., Escobar, E., Liu, E. T., Yamane, H. K.
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<strong>Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6.</strong>
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Nature 373: 623-626, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7854420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7854420</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7854420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/373623a0" target="_blank">Full Text</a>]
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<a id="Zhang2012" class="mim-anchor"></a>
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Zhang, Z., Lee, J. C., Lin, L., Olivas, V., Au, V., LaFramboise, T., Abdel-Rahman, M., Wang, X., Levine, A. D., Rho, J. K., Choi, Y. J., Choi, C.-M., and 18 others.
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<strong>Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer.</strong>
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Nature Genet. 44: 852-860, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22751098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22751098</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22751098[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22751098" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng.2330" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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Ada Hamosh - updated : 08/10/2020
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<span class="mim-text-font">
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Ada Hamosh - updated : 09/29/2016<br>Ada Hamosh - updated : 04/14/2014<br>Ada Hamosh - updated : 2/26/2013<br>Paul J. Converse - updated : 3/1/2012<br>Paul J. Converse - updated : 3/14/2008<br>Marla J. F. O'Neill - updated : 4/12/2005<br>Paul J. Converse - updated : 8/8/2001
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 8/18/1993
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alopez : 09/25/2020
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alopez : 08/10/2020<br>alopez : 08/10/2020<br>alopez : 08/10/2020<br>carol : 09/30/2016<br>alopez : 09/29/2016<br>alopez : 04/14/2014<br>alopez : 3/4/2013<br>terry : 2/26/2013<br>mgross : 3/5/2012<br>terry : 3/1/2012<br>alopez : 4/4/2011<br>mgross : 3/14/2008<br>tkritzer : 4/12/2005<br>alopez : 11/17/2003<br>mgross : 8/8/2001<br>mark : 6/10/1996<br>terry : 3/7/1995<br>carol : 3/6/1995<br>carol : 8/30/1993<br>carol : 8/18/1993
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<strong>*</strong> 109135
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AXL RECEPTOR TYROSINE KINASE; AXL
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ONCOGENE AXL<br />
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AXL TRANSFORMING GENE
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<strong><em>HGNC Approved Gene Symbol: AXL</em></strong>
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Cytogenetic location: 19q13.2
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<span class="small">(from NCBI)</span>
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<strong>Cloning and Expression</strong>
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<p>In an effort to determine genes involved in the progression of chronic myelogenous leukemia (CML; 608232) to acute-phase leukemia, Liu et al. (1988) identified a transforming gene in the DNAs of 2 patients with this disorder. O'Bryan et al. (1991) found by molecular cloning and characterization of this gene, which they termed AXL (from the Greek word 'anexelekto,' or uncontrolled), that it is a receptor tyrosine kinase with a structure novel among tyrosine kinases. They showed that the AXL protein is capable of transforming NIH 3T3 cells. Furthermore, its transforming capacity results from overexpression of AXL mRNA rather than from structural mutation. </p><p>Janssen et al. (1991) independently found transforming activity by a tumorigenicity assay using NIH 3T3 cells transfected with DNA from a patient with a chronic myeloproliferative disorder. They reported the cDNA cloning of the corresponding oncogene, which they designated UFO, in allusion to the unidentified function of the protein. Nucleotide sequence analysis revealed a 2,682-bp open reading frame capable of directing the synthesis of an 894-amino acid polypeptide. It was evolutionarily conserved among vertebrate species. The predicted protein showed features characteristic of a transmembrane receptor with tyrosine kinase activity. The gene was transcribed into two 5.0-kb and 3.2-kb mRNAs in human bone marrow and human tumor cell lines. </p>
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<p>The transforming activity of AXL demonstrates that the receptor can drive cellular proliferation. Although the function of AXL in nontransformed cells and tissues was unknown, Varnum et al. (1995) suspected that it may involve the stimulation of cell proliferation in response to an appropriate signal, i.e., a ligand that activates the receptor. Varnum et al. (1995) purified an AXL stimulatory factor and identified it as the product of the growth arrest-specific gene-6 (GAS6; 600441) (Manfioletti et al., 1993). </p><p>Loss of function of the 3 TAM receptors, Tyro3 (600341), Axl, and Mer (MERTK; 604705), results in profound dysregulation of the immune response in mice (see ANIMAL MODEL). By analyzing TAM function in the dendritic cell subset of mouse antigen-presenting cells, Rothlin et al. (2007) found that TAM inhibited inflammation through an essential stimulator of inflammation, Ifnar (107450), and its associated transcription factor, Stat1 (600555). Toll-like receptor (TLR; see 601194) induction of Ifnar-Stat1 signaling upregulated the TAM system, which, in turn, induced the cytokine and TLR suppressors Socs1 (603597) and Socs3 (604176). Rothlin et al. (2007) concluded that cytokine-dependent activation of TAM signaling diverts a proinflammatory pathway to provide an intrinsic feedback inhibitor of both TLR- and cytokine-driven immune responses. </p><p>Pseudotypes are viral particles that carry the genome of one virus and 1 or more proteins of another virus (Temperton and Wright, 2009). Morizono et al. (2011) studied the infectivity of lentivirus pseudotypes lacking envelope binding and observed residual high infectivity for some cell types. The retained infectivity was conferred by soluble bovine protein S in the culture medium. Morizono et al. (2011) showed that bovine protein S and its human homolog, GAS6, mediated binding of the virus to target cells by bridging virion envelope phosphatidylserine to AXL present on target cells. </p><p>Paolino et al. (2014) demonstrated that genetic deletion of the E3 ubiquitin ligase CBLB (604491) or targeted inactivation of its E3 ligase activity licenses natural killer (NK) cells to spontaneously reject metastatic tumors. The TAM tyrosine kinase receptors TYRO3, AXL, and MERTK were identified as ubiquitylation substrates for CBLB. Treatment of wildtype NK cells with a small molecule TAM kinase inhibitor conferred therapeutic potential, efficiently enhancing antimetastatic NK cell activity in vivo. Oral or intraperitoneal administration using this TAM inhibitor markedly reduced murine mammary cancer and melanoma metastases dependent on NK cells. Paolino et al. (2014) further reported that the anticoagulant warfarin exerts antimetastatic activity in mice via Cblb/TAM receptors in NK cells, providing a molecular explanation for the effect of warfarin to reduce tumor metastases in rodent models. Paolino et al. (2014) concluded that this novel TAM/CBLB inhibitory pathway shows that it might be possible to develop a 'pill' that awakens the innate immune system to kill cancer metastases. </p><p>Fourgeaud et al. (2016) demonstrated that the TAM receptor tyrosine kinases Mer and Axl regulate the microglial functions of damage sensing and routine noninflammatory clearance of dead brain cells. Fourgeaud et al. (2016) found that adult mice deficient in microglial Mer and Axl exhibit a marked accumulation of apoptotic cells specifically in neurogenic regions of the central nervous system (CNS), and that microglial phagocytosis of the apoptotic cells generated during adult neurogenesis is normally driven by both TAM receptor ligands Gas6 and protein S (176880). Using live 2-photon imaging, the authors demonstrated that the microglial response to brain damage is also TAM-regulated, as TAM-deficient microglia display reduced process motility and delayed convergence to sites of injury. Fourgeaud et al. (2016) also showed that microglial expression of Axl is prominently upregulated in the inflammatory environment that develops in a mouse model of Parkinson disease (168600). Fourgeaud et al. (2016) concluded that these results established TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease. </p><p>Using single-cell RNA sequencing in human and mouse non-small-cell lung cancers, Maier et al. (2020) identified a cluster of dendritic cells (DCs) that they named 'mature dendritic cells enriched in immunoregulatory molecules' (mregDCs), owing to their coexpression of immunoregulatory genes and maturation genes. Maier et al. (2020) found that the mregDC program is expressed by canonical DC1s and DC2s upon uptake of tumor antigens and further found that upregulation of PDL1 (605402), a key checkpoint molecule, in mregDCs is induced by the receptor tyrosine kinase AXL, while upregulation of interleukin-12 (IL12; see 161560) depends strictly on interferon-gamma (IFNG; 147570) and is controlled negatively by IL4 (147780) signaling. Blocking IL4 enhances IL12 production by tumor antigen-bearing mregDC1s, expands the pool of tumor-infiltrating effector T cells, and reduces tumor burden. Maier et al. (2020) concluded that they uncovered a regulatory module associated with tumor-antigen uptake that reduces DC1 functionality in human and mouse cancers. </p>
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<strong>Mapping</strong>
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<p>By fluorescence in situ hybridization, O'Bryan et al. (1991) localized the AXL gene to 19q13.2. </p><p>By nonisotopic in situ hybridization, Janssen et al. (1991) mapped the AXL gene to 19q13.1. </p>
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<p>Zhang et al. (2012) reported increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR (131550)-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR T790M alteration (131550.0006) or MET activation. Genetic or pharmacologic inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 (600441) was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to tyrosine kinase inhibitors. </p>
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<p>Regulation of lymphocyte numbers is mediated by cytokines signaling through receptors coupled to cytoplasmic protein-tyrosine kinases. Lu and Lemke (2001) generated mice deficient in Mertk (604705), Axl, and Tyro3 (600341). Like their ligands, GAS6 and PROS1 (176880), these receptors are widely expressed in monocytes and macrophages but not in B or T lymphocytes. Although the peripheral lymphoid organs of mutant mice were indistinguishable from those of wildtype mice at birth, by 4 weeks of age spleens and lymph nodes grew at elevated rates. This was primarily due to the hyperproliferation of constitutively activated B and T cells, particularly CD4-positive T cells, with ectopic colonies in every adult organ examined. All triple mutants developed autoimmunity with symptoms histologically similar to human rheumatoid arthritis (180300), pemphigus vulgaris (169610), and systemic lupus erythematosus (152700), and were characterized by antibodies against normal cellular antigens, including phospholipids and double-stranded DNA. Females were particularly prone to thromboses and recurrent fetal loss. Flow cytometric analysis demonstrated that wildtype B and T cells underwent multiple rounds of cell division after injection into mutant mice and that their antigen-presenting cells expressed elevated levels of activation markers. Lu and Lemke (2001) proposed that the cells that initiate lymphoproliferation and autoimmunity in the Tyro3 family mutants were the macrophages and dendritic cells that normally express the 3 receptor genes. </p><p>Angelillo-Scherrer et al. (2005) generated mice lacking 1 of the 3 Gas6 receptors: Tyro3, Axl, or Mertk. Loss of any 1 of the Gas6 receptors or delivery of a soluble extracellular domain of Axl that traps Gas6 protected the mice against life-threatening thrombosis. Loss of a Gas6 receptor did not prevent initial platelet aggregation but impaired subsequent stabilization of platelet aggregates, at least in part by reducing outside-in signaling and platelet granule secretion. Gas6, through its receptors, activated PI3K and Akt (see 164730) and stimulated tyrosine phosphorylation of the beta-3 integrin (173470), thereby amplifying outside-in signaling via alpha-IIb (607759)-beta-3. </p>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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|
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</h4>
|
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<p />
|
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</div>
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|
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<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Angelillo-Scherrer, A., Burnier, L., Flores, N., Savi, P., DeMol, M., Schaeffer, P., Herbert, J.-M., Lemke, G., Goff, S. P., Matsushima, G. K., Earp, H. S., Vesin, C., Hoylaerts, M. F., Plaisance, S., Collen, D., Conway, E. M., Wehrle-Haller, B., Carmeliet, P.
|
|
<strong>Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy.</strong>
|
|
J. Clin. Invest. 115: 237-246, 2005.
|
|
|
|
|
|
[PubMed: 15650770]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI22079]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fourgeaud, L., Traves, P. G., Tufail, Y., Leal-Bailey, H., Lew, E. D., Burrola, P. G., Callaway, P., Zagorska, A., Rothlin, C. V., Nimmerjahn, A., Lemke, G.
|
|
<strong>TAM receptors regulate multiple features of microglial physiology.</strong>
|
|
Nature 532: 240-244, 2016.
|
|
|
|
|
|
[PubMed: 27049947]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature17630]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Janssen, J. W. G., Schulz, A. S., Steenvoorden, A. C. M., Schmidberger, M., Strehl, S., Ambros, P. F., Bartram, C. R.
|
|
<strong>A novel putative tyrosine kinase receptor with oncogenic potential.</strong>
|
|
Oncogene 6: 2113-2120, 1991.
|
|
|
|
|
|
[PubMed: 1834974]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Liu, E., Hjelle, B., Bishop, J. M.
|
|
<strong>Transforming genes in chronic myelogenous leukemia.</strong>
|
|
Proc. Nat. Acad. Sci. 85: 1952-1956, 1988.
|
|
|
|
|
|
[PubMed: 3279421]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.85.6.1952]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lu, Q., Lemke, G.
|
|
<strong>Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family.</strong>
|
|
Science 293: 306-311, 2001.
|
|
|
|
|
|
[PubMed: 11452127]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1061663]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maier, B., Leader, A. M., Chen, S. T., Tung, N., Chang, C., LeBerichel, J., Chudnovskiy, A., Maskey, S., Walker, L., Finnigan, J. P., Kirkling, M. E., Reizis, B., and 11 others.
|
|
<strong>A conserved dendritic-cell regulatory program limits antitumour immunity.</strong>
|
|
Nature 580: 257-262, 2020. Note: Erratum: Nature 582: E17, 2020. Electronic Article.
|
|
|
|
|
|
[PubMed: 32269339]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41586-020-2134-y]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Manfioletti, G., Brancolini, C., Avanzi, G., Schneider, C.
|
|
<strong>The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade.</strong>
|
|
Molec. Cell. Biol. 13: 4976-4985, 1993.
|
|
|
|
|
|
[PubMed: 8336730]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/mcb.13.8.4976-4985.1993]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morizono, K., Xie, Y., Olafsen, T., Lee, B., Dasgupta, A., Wu, A. M., Chen, I. S. Y.
|
|
<strong>The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry.</strong>
|
|
Cell Host Microbe 9: 286-298, 2011.
|
|
|
|
|
|
[PubMed: 21501828]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.chom.2011.03.012]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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O'Bryan, J. P., Frye, R. A., Cogswell, P. C., Neubauer, A., Kitch, B., Prokop, C., Espinosa, R., III, Le Beau, M. M., Earp, H. S., Liu, E. T.
|
|
<strong>Axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase.</strong>
|
|
Molec. Cell. Biol. 11: 5016-5031, 1991.
|
|
|
|
|
|
[PubMed: 1656220]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/mcb.11.10.5016-5031.1991]
|
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</p>
|
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</li>
|
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|
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<li>
|
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<p class="mim-text-font">
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Paolino, M., Choidas, A., Wallner, S., Pranjic, B. Uribesalgo, I., Loeser, S., Jamieson, A. M., Langdon, W. Y., Ikeda, F., Fededa, J. P., Cronin, S. J., Nitsch, R., and 12 others.
|
|
<strong>The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells.</strong>
|
|
Nature 507: 508-512, 2014.
|
|
|
|
|
|
[PubMed: 24553136]
|
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|
|
|
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[Full Text: https://doi.org/10.1038/nature12998]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Rothlin, C. V., Ghosh, S., Zuniga, E. I., Oldstone, M. B. A., Lemke, G.
|
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<strong>TAM receptors are pleiotropic inhibitors of the innate immune response.</strong>
|
|
Cell 131: 1124-1136, 2007.
|
|
|
|
|
|
[PubMed: 18083102]
|
|
|
|
|
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[Full Text: https://doi.org/10.1016/j.cell.2007.10.034]
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</p>
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</li>
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|
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<li>
|
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<p class="mim-text-font">
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Temperton, N. J., Wright, E.
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<strong>Retroviral pseudotypes. In: Encyclopedia of Life Sciences.</strong>
|
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Chichester, England: John Wiley & Sons, Ltd. 2009.
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|
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</p>
|
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</li>
|
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<li>
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<p class="mim-text-font">
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Varnum, B. C., Young, C., Elliott, G., Garcia, A., Bartley, T. D., Fridell, Y.-W., Hunt, R. W., Trail, G., Clogston, C., Toso, R. J., Yanagihara, D., Bennett, L., Sylber, M., Merewether, L. A., Tseng, A., Escobar, E., Liu, E. T., Yamane, H. K.
|
|
<strong>Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6.</strong>
|
|
Nature 373: 623-626, 1995.
|
|
|
|
|
|
[PubMed: 7854420]
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[Full Text: https://doi.org/10.1038/373623a0]
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</p>
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</li>
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Zhang, Z., Lee, J. C., Lin, L., Olivas, V., Au, V., LaFramboise, T., Abdel-Rahman, M., Wang, X., Levine, A. D., Rho, J. K., Choi, Y. J., Choi, C.-M., and 18 others.
|
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<strong>Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer.</strong>
|
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Nature Genet. 44: 852-860, 2012.
|
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[PubMed: 22751098]
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[Full Text: https://doi.org/10.1038/ng.2330]
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Ada Hamosh - updated : 08/10/2020<br>Ada Hamosh - updated : 09/29/2016<br>Ada Hamosh - updated : 04/14/2014<br>Ada Hamosh - updated : 2/26/2013<br>Paul J. Converse - updated : 3/1/2012<br>Paul J. Converse - updated : 3/14/2008<br>Marla J. F. O'Neill - updated : 4/12/2005<br>Paul J. Converse - updated : 8/8/2001
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