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<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="BtkHe15c9wYDyBrfdl26gtymlT4YfSHWq1kUSrBuOyDpTF5l4Is3sr3ySn9km6d4">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="BtkHe15c9wYDyBrfdl26gtymlT4YfSHWq1kUSrBuOyDpTF5l4Is3sr3ySn9km6d4">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="BtkHe15c9wYDyBrfdl26gtymlT4YfSHWq1kUSrBuOyDpTF5l4Is3sr3ySn9km6d4">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="BtkHe15c9wYDyBrfdl26gtymlT4YfSHWq1kUSrBuOyDpTF5l4Is3sr3ySn9km6d4">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="BtkHe15c9wYDyBrfdl26gtymlT4YfSHWq1kUSrBuOyDpTF5l4Is3sr3ySn9km6d4">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="17040207">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://portlandpress.com/biochemj/article-lookup/doi/10.1042/BJ20061153"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=7898&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=17040207&amp;db=pubmed&amp;nlmid=2984726R"
title="See full text options at Silverchair Information Systems"
data-ga-category="full_text"
data-ga-action="Silverchair Information Systems"
data-ga-label="17040207"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--portlandpress.com-images-pubmed-logo.png" alt="Silverchair Information Systems full text link"><span class="text">
Silverchair Information Systems
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/17040207/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=17040207&amp;db=pubmed&amp;nlmid=2984726R"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="17040207"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/17040207/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/17040207/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="17040207" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F17040207%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="BtkHe15c9wYDyBrfdl26gtymlT4YfSHWq1kUSrBuOyDpTF5l4Is3sr3ySn9km6d4"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
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The Dictyostelium discoideum genome uncovers seven cyclic nucleotide PDEs (phosphodiesterases), of which six have been characterized previously and the seventh is characterized in the present paper. Three enzymes belong to the ubiquitous class I PDEs, common in all eukaryotes, whereas four enzymes belong to the rare class II PDEs that are present in bacteria and lower eukaryotes. Since all D. discoideum PDEs are now characterized we have calculated the contribution of each enzyme in the degradation of the three important pools of cyclic nucleotides: (i) extracellular cAMP that induces chemotaxis during aggregation and differentiation in slugs; (ii) intracellular cAMP that mediates development; and (iii) intracellular cGMP that mediates chemotaxis. It appears that each cyclic nucleotide pool is degraded by a combination of enzymes that have different affinities, allowing a broad range of substrate concentrations to be degraded with first-order kinetics. Extracellular cAMP is degraded predominantly by the class II high-affinity enzyme DdPDE1 and its close homologue DdPDE7, and in the multicellular stage also by the low-affinity transmembrane class I enzyme DdPDE4. Intracellular cAMP is degraded by the DdPDE2, a class I enzyme regulated by histidine kinase/phospho-relay, and by the cAMP-/cGMP-stimulated class II DdPDE6. Finally, basal intracellular cGMP is degraded predominantly by the high-affinity class I DdPDE3, while the elevated cGMP levels that arise after receptor stimulation are degraded predominantly by a cGMP-stimulated cGMP-specific class II DdPDE5. The analysis shows that the combination of enzymes is tuned to keep the concentration and lifetime of the substrate within a functional range.
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<p> Figure 1. The PDE family of <i> D.… </i> </p>
</strong>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 1. The PDE family of <i> D. discoideum </i> </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A </b> ) Seven PDEs have been… </p></div>
</div>
<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 1. The PDE family of <i>D. discoideum</i>
</strong>
<div class="figure-caption-contents">(<b>A</b>) Seven PDEs have been recognized and identified in the completed genome of <i>D. discoideum</i>. The enzymes belong to the class I enzymes prevalent in higher eukaryotes, or to the class II enzymes that are present in lower eukaryotes and some bacteria. Based on bootstrap data of phylogenetic cluster analysis of type II enzymes, the class II enzymes are recognized as catalytic PDEs or catalytic metallo-β-lactamases. The localization and activity of the seven enzymes are regulated by signal sequences, transmembrane segments, a response regulator domain or cNB domains. (<b>B</b>) Cluster analysis of the catalytic domains of class II enzymes from prokaryotes and lower eukaryotes. All nodes have bootstrap values above 70%, except for the nodes indicated by the small white ovals. Bootstrap values of the inner nodes are indicated. These bootstrap values and the length of the catalytic domain suggest two main groups, metallo-β-lactamases and PDEs; the latter may consist of two subgroups. The species abbreviations, gene identifiers and taxonomy are: Dh, <i>Debaryomyces hansenii</i>, gi|50424793, Eukaryota, Fungi; Cal, <i>Candida albicans</i>, gi|7548341, Eukaryota, Fungi; Kl, <i>Kluyveromyces lactis</i>, gi|50307193, Eukaryota, Fungi; Eg, <i>Eremothecium gossypii</i>, gi|44984787, Eukaryota, Fungi; Cg, <i>Candida glabrata</i>, gi|49526440, Eukaryota, Fungi; Sc, <i>Saccharomyces cerevisiae</i>, gi|6321189, Eukaryota, Fungi; Yl, <i>Yarrowia lipolytica</i>, gi|50554561, Eukaryota, Fungi; Nc, <i>Neurospora crassa</i>, gi|85086599, Eukaryota, Fungi; Sp, <i>Schizosaccharomyces pombe</i>, gi|3581909, Eukaryota, Fungi; Dd, <i>D. discoideum</i>; DdPDE1, gi|84080, DdPDE5, gi|21069535, DdPDE6, gi|66819225, DdPDE7, gi|66805301, Eukaryota, Mycetozoa; Lp, <i>Legionella pneumophila</i>, gi|53754670, Bacteria, Proteobacteria; Pa, <i>Pseudoalteromonas atlantica</i>, gi|76793857, Bacteria, Proteobacteria; Yp, <i>Yersinia pseudotuberculosis</i>, gi|77629947, Bacteria, Proteobacteria; Vf, <i>Vibrio fischeri</i>, gi|59711863, Bacteria, Proteobacteria; Ddβ-lactamase, <i>D. discoideum</i>, gi|66802803, Eukaryota, Mycetozoa; Mm, <i>Magnetospirillum magnetotacticum</i>, gi|23012958, Bacteria, Proteobacteria; Cau, <i>Chloroflexus aurantiacus</i>, gi |76165595, Bacteria, Chloroflexi; Tt, <i>Tetrahymena thermophila</i>; Tt1, gi|89287508, Tt2, gi|89296516, Eukaryota, Alveolata; Li, <i>Leptospira interrogans</i>, gi|45657830, Bacteria, Spirochaetes.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="1"
data-label-slug="figure-2">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090e/1783984/530b776b87ba/bic982i002.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-1"
role="button"
data-image-width="453"
data-image-height="287"
data-image-alt="Figure 2"
data-pmc-id="PMC1783984"
data-figure-id="F2">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-1"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090e/1783984/8cab39bac924/bic982i002.gif"
alt="Figure 2" />
</a>
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<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="287">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 2. Alignment of DdPDE1 and DdPDE7 </p>
</strong>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 2. Alignment of DdPDE1 and DdPDE7 </p>
</strong>
<div class="figure-caption-contents"><p> The deduced amino acid sequence of DdPDE1 and… </p></div>
</div>
<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 2. Alignment of DdPDE1 and DdPDE7
</strong>
<div class="figure-caption-contents">The deduced amino acid sequence of DdPDE1 and DdPDE7. Underlined are the predicted signal sequences with cleavage between amino acid 17 and 18 for DdPDE1 and 23 and 24 for DdPDE7. A potential hydrophobic transmembrane segment is indicated in small italic letters. The asterisk indicates a potential GPI anchor.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="2"
data-label-slug="figure-3">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090e/1783984/c41c7422632a/bic982i003.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-2"
role="button"
data-image-width="486"
data-image-height="556"
data-image-alt="Figure 3"
data-pmc-id="PMC1783984"
data-figure-id="F3">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-2"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090e/1783984/b64e9a2968ac/bic982i003.gif"
alt="Figure 3" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="486">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="556">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 3. Initial characterization of DdPDE7 </p>
</strong>
<div class="figure-caption-contents"><p> (… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 3. Initial characterization of DdPDE7 </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A </b> ) Inhibition by IBMX and DTT of… </p></div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 3. Initial characterization of DdPDE7
</strong>
<div class="figure-caption-contents">(<b>A</b>) Inhibition by IBMX and DTT of PDE activity at the surface of wild-type AX3 cells and UK7 cells with a deletion of DdPDE1 that had been starved for 5 h. The activity in the absence of inhibitors is set at 100% (2950 fmol/min per 10<sup>7</sup> cells in AX3 and 61 fmol/min per 10<sup>7</sup> cells in UK7). The results show that the residual PDE activity exposed on UK7 cells is inhibited strongly by DTT and only partly by IBMX. (<b>B</b>) Over-expression of DdPDE7 in UK7 cells reveal enhanced activity both on the cell surface and secreted in the medium.</div>
</figcaption>
</figure>
<figure class="figure-item "
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itemprop="associatedMedia"
data-slide-index="3"
data-label-slug="figure-4">
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090e/1783984/8b5cf1c621f9/bic982i004.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-3"
role="button"
data-image-width="486"
data-image-height="426"
data-image-alt="Figure 4"
data-pmc-id="PMC1783984"
data-figure-id="F4">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-3"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090e/1783984/329558eeff7c/bic982i004.gif"
alt="Figure 4" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="486">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="426">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 4. Kinetics of DdPDE7 </p>
</strong>
<div class="figure-caption-contents"><p> UK7 cells… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 4. Kinetics of DdPDE7 </p>
</strong>
<div class="figure-caption-contents"><p> UK7 cells that had been starved for 5 h were… </p></div>
</div>
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 4. Kinetics of DdPDE7
</strong>
<div class="figure-caption-contents">UK7 cells that had been starved for 5 h were incubated with different concentrations of cAMP or cGMP. The hydrolysis was measured after 30 min and expressed as an EadyHofstee plot in the main figure and as a Hill plot in the inset. The dotted lines were fitted for MichaelisMenten kinetics using linear regression, while the straight lines were fitted for negative co-operativity using the Hill equation. The deduced kinetic constants for the Hill equation are, for cAMP apparent <i>K</i><sub>m</sub>=12.5 μm, <i>V</i><sub>max</sub>=28 pmol/min per 10<sup>7</sup>cells, Hill coefficient=0.79, and for cGMP, apparent <i>K</i><sub>m</sub>=36 μm, <i>V</i><sub>max</sub>=72 pmol/min per 10<sup>7</sup>cells and Hill coefficient=0.9.</div>
</figcaption>
</figure>
<figure class="figure-item "
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itemprop="associatedMedia"
data-slide-index="4"
data-label-slug="figure-5">
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090e/1783984/aef3e23de9fe/bic982i005.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-4"
role="button"
data-image-width="506"
data-image-height="194"
data-image-alt="Figure 5"
data-pmc-id="PMC1783984"
data-figure-id="F5">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-4"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090e/1783984/eed63db9afa0/bic982i005.gif"
alt="Figure 5" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="506">
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="194">
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 5. DdPDE7 activity during development </p>
</strong>
<div class="figure-caption-contents"><p> (… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 5. DdPDE7 activity during development </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A </b> ), UK7/ <i> regA </i> <sup> </sup> cells were starved… </p></div>
</div>
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 5. DdPDE7 activity during development
</strong>
<div class="figure-caption-contents">(<b>A</b>), UK7/<i>regA</i><sup></sup> cells were starved on plates for the times indicated, harvested, washed and assayed for cell surface cAMP hydrolysis using 10 nM [<sup>3</sup>H]cAMP. Cell aggregation was observed at 6 h of development, and tight aggregates and slugs were observed at 9 h; development was arrested at this stage. (<b>B</b>) Activity of DdPDE1, DdPDE4 and DdPDE7 during development, deduced from (<b>A</b>) for DdPDE7, and from Figure 6 in Bader et al. [28] for DdPDE1 and DdPDE4.</div>
</figcaption>
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itemprop="associatedMedia"
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data-label-slug="figure-6">
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itemprop="contentUrl"
aria-describedby="figure-caption-5"
role="button"
data-image-width="506"
data-image-height="424"
data-image-alt="Figure 6"
data-pmc-id="PMC1783984"
data-figure-id="F6">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-5"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090e/1783984/17b3223672d1/bic982i006.gif"
alt="Figure 6" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="506">
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<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 6. Contribution of the seven PDEs… </p>
</strong>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 6. Contribution of the seven PDEs to the hydrolysis of three cyclic nucleotide pools </p>
</strong>
</div>
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 6. Contribution of the seven PDEs to the hydrolysis of three cyclic nucleotide pools
</strong>
<div class="figure-caption-contents">(<b>A</b>) Extracellular cAMP during aggregation; (<b>B</b>) extracellular cAMP in slugs; (<b>C</b>) intracellular cAMP during aggregation; (<b>D</b>) intracellular cGMP during aggregation. The activity of each enzyme was calculated at different substrate concentrations using the equations presented in the Experimental procedures section and the kinetic constants as presented in Table 1. From these activities we calculated the half-life of degradation of the indicated substrate concentration, and the relative contribution of the participating enzymes in the degradation of substrate. The arrows indicate the range of substrate concentrations that have been measured <i>in vivo</i> during cell stimulation.</div>
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