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 bind...

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Main Authors: Carlessi, Rodrigo, Levin-Salomon, V., Ciprut, S., Bialik, S., Berissi, H., Albeck, S., Peleg, Y., Kimchi, A.
Format: Journal Article
Published: 2011
Online Access:http://hdl.handle.net/20.500.11937/47501
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author Carlessi, Rodrigo
Levin-Salomon, V.
Ciprut, S.
Bialik, S.
Berissi, H.
Albeck, S.
Peleg, Y.
Kimchi, A.
author_facet Carlessi, Rodrigo
Levin-Salomon, V.
Ciprut, S.
Bialik, S.
Berissi, H.
Albeck, S.
Peleg, Y.
Kimchi, A.
author_sort Carlessi, Rodrigo
building Curtin Institutional Repository
collection Online Access
description 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. © 2011 European Molecular Biology Organization.
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institution Curtin University Malaysia
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last_indexed 2025-11-14T09:34:38Z
publishDate 2011
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spelling curtin-20.500.11937-475012023-02-22T06:24:18Z GTP binding to the ROC domain of DAP-kinase regulates its function through intramolecular signalling Carlessi, Rodrigo Levin-Salomon, V. Ciprut, S. Bialik, S. Berissi, H. Albeck, S. Peleg, Y. Kimchi, 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. © 2011 European Molecular Biology Organization. 2011 Journal Article http://hdl.handle.net/20.500.11937/47501 10.1038/embor.2011.126 unknown
spellingShingle Carlessi, Rodrigo
Levin-Salomon, V.
Ciprut, S.
Bialik, S.
Berissi, H.
Albeck, S.
Peleg, Y.
Kimchi, A.
GTP binding to the ROC domain of DAP-kinase regulates its function through intramolecular signalling
title GTP binding to the ROC domain of DAP-kinase regulates its function through intramolecular signalling
title_full GTP binding to the ROC domain of DAP-kinase regulates its function through intramolecular signalling
title_fullStr GTP binding to the ROC domain of DAP-kinase regulates its function through intramolecular signalling
title_full_unstemmed GTP binding to the ROC domain of DAP-kinase regulates its function through intramolecular signalling
title_short GTP binding to the ROC domain of DAP-kinase regulates its function through intramolecular signalling
title_sort gtp binding to the roc domain of dap-kinase regulates its function through intramolecular signalling
url http://hdl.handle.net/20.500.11937/47501