GTP binding to the ROC domain of DAP‐kinase regulates its function through intramolecular signalling
Identifieur interne : 000310 ( Main/Exploration ); précédent : 000309; suivant : 000311GTP binding to the ROC domain of DAP‐kinase regulates its function through intramolecular signalling
Auteurs : Rodrigo Carlessi [Israël] ; Vered Levin-Salomon [Israël] ; Sara Ciprut [Israël] ; Shani Bialik [Israël] ; Hanna Berissi [Israël] ; Shira Albeck ; Yoav Peleg ; Adi Kimchi [Israël]Source :
- EMBO reports [ 1469-221X ] ; 2011-09.
Abstract
Death‐associated protein kinase (DAPk) was recently suggested by sequence homology to be a member of the ROCO family of proteins. Here, we show that DAPk has a functional ROC (Ras of complex proteins) domain that mediates homo‐oligomerization and GTP binding through a defined P‐loop motif. Upon binding to GTP, the ROC domain negatively regulates the catalytic activity of DAPk and its cellular effects. Mechanistically, GTP binding enhances an inhibitory autophosphorylation at a distal site that suppresses kinase activity. This study presents a new mechanism of intramolecular signal transduction, by which GTP binding operates in cis to affect the catalytic activity of a distal domain in the protein.
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DOI: 10.1038/embor.2011.126
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sort="Albeck, Shira" uniqKey="Albeck S" first="Shira" last="Albeck">Shira Albeck</name><affiliation><wicri:noCountry code="subField">Rehovot</wicri:noCountry></affiliation></author><author><name sortKey="Peleg, Yoav" sort="Peleg, Yoav" uniqKey="Peleg Y" first="Yoav" last="Peleg">Yoav Peleg</name><affiliation><wicri:noCountry code="subField">Rehovot</wicri:noCountry></affiliation></author><author><name sortKey="Kimchi, Adi" sort="Kimchi, Adi" uniqKey="Kimchi A" first="Adi" last="Kimchi">Adi Kimchi</name><affiliation wicri:level="1"><country xml:lang="fr">Israël</country><wicri:regionArea>Department of Molecular Genetics, Weizmann Institute of Science, 76100, Rehovot</wicri:regionArea><wicri:noRegion>Rehovot</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">EMBO reports</title><idno type="ISSN">1469-221X</idno><idno type="eISSN">1469-3178</idno><imprint><publisher>John Wiley & Sons, Ltd</publisher><pubPlace>Chichester, UK</pubPlace><date type="published" when="2011-09">2011-09</date><biblScope unit="volume">12</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="917">917</biblScope><biblScope unit="page" to="923">923</biblScope></imprint><idno type="ISSN">1469-221X</idno></series><idno type="istex">E63CE78FCB98C0272C4228C7566D78F8F05F013C</idno><idno type="DOI">10.1038/embor.2011.126</idno><idno type="ArticleID">EMBR2011126</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1469-221X</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Death‐associated protein kinase (DAPk) was recently suggested by sequence homology to be a member of the ROCO family of proteins. Here, we show that DAPk has a functional ROC (Ras of complex proteins) domain that mediates homo‐oligomerization and GTP binding through a defined P‐loop motif. Upon binding to GTP, the ROC domain negatively regulates the catalytic activity of DAPk and its cellular effects. Mechanistically, GTP binding enhances an inhibitory autophosphorylation at a distal site that suppresses kinase activity. This study presents a new mechanism of intramolecular signal transduction, by which GTP binding operates in cis to affect the catalytic activity of a distal domain in the protein.</div></front></TEI><affiliations><list><country><li>Israël</li></country></list><tree><noCountry><name sortKey="Albeck, Shira" sort="Albeck, Shira" uniqKey="Albeck S" first="Shira" last="Albeck">Shira Albeck</name><name sortKey="Peleg, Yoav" sort="Peleg, Yoav" uniqKey="Peleg Y" first="Yoav" last="Peleg">Yoav Peleg</name></noCountry><country name="Israël"><noRegion><name sortKey="Carlessi, Rodrigo" sort="Carlessi, Rodrigo" uniqKey="Carlessi R" first="Rodrigo" last="Carlessi">Rodrigo Carlessi</name></noRegion><name sortKey="Berissi, Hanna" sort="Berissi, Hanna" uniqKey="Berissi H" first="Hanna" last="Berissi">Hanna Berissi</name><name sortKey="Bialik, Shani" sort="Bialik, Shani" uniqKey="Bialik S" first="Shani" last="Bialik">Shani Bialik</name><name sortKey="Ciprut, Sara" sort="Ciprut, Sara" uniqKey="Ciprut S" first="Sara" last="Ciprut">Sara Ciprut</name><name sortKey="Kimchi, Adi" sort="Kimchi, Adi" uniqKey="Kimchi A" first="Adi" last="Kimchi">Adi Kimchi</name><name sortKey="Levin Alomon, Vered" sort="Levin Alomon, Vered" uniqKey="Levin Alomon V" first="Vered" last="Levin-Salomon">Vered Levin-Salomon</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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