GTP binding to the ROC domain of DAP-kinase regulates its function through intramolecular signalling
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2011 |
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| Erschienen: |
2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
EMBO reports - 12(2011), 9 vom: 01. Sept., Seite 917-23 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Carlessi, Rodrigo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.02.2012 Date Revised 20.10.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/embor.2011.126 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM209788445 |
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| 245 | 1 | 0 | |a GTP binding to the ROC domain of DAP-kinase regulates its function through intramolecular signalling |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Apoptosis Regulatory Proteins |2 NLM | |
| 650 | 7 | |a Guanosine Triphosphate |2 NLM | |
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| 650 | 7 | |a Death-Associated Protein Kinases |2 NLM | |
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| 650 | 7 | |a Calcium-Calmodulin-Dependent Protein Kinases |2 NLM | |
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| 650 | 7 | |a GTP-Binding Proteins |2 NLM | |
| 650 | 7 | |a EC 3.6.1.- |2 NLM | |
| 650 | 7 | |a Oncogene Protein p21(ras) |2 NLM | |
| 650 | 7 | |a EC 3.6.5.2 |2 NLM | |
| 700 | 1 | |a Levin-Salomon, Vered |e verfasserin |4 aut | |
| 700 | 1 | |a Ciprut, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Bialik, Shani |e verfasserin |4 aut | |
| 700 | 1 | |a Berissi, Hanna |e verfasserin |4 aut | |
| 700 | 1 | |a Albeck, Shira |e verfasserin |4 aut | |
| 700 | 1 | |a Peleg, Yoav |e verfasserin |4 aut | |
| 700 | 1 | |a Kimchi, Adi |e verfasserin |4 aut | |
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