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GTP binding to the ROC domain of DAP-kinase regulates its function through intramolecular signalling.

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.

SUBMITTER: Carlessi R

PROVIDER: S-EPMC3166453 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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GTP binding to the ROC domain of DAP-kinase regulates its function through intramolecular signalling.

Carlessi Rodrigo R Levin-Salomon Vered V Ciprut Sara S Bialik Shani S Berissi Hanna H Albeck Shira S Peleg Yoav Y Kimchi Adi A

EMBO reports 20110901 9

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 s ...[more]

PMID: 21738225

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