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

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Authors
Carlessi, Rodrigo
Levin-Salomon, V.
Ciprut, S.
Bialik, S.
Berissi, H.
Albeck, S.
Peleg, Y.
Kimchi, A.
Date
2011
Type
Journal Article

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Carlessi, R. and Levin-Salomon, V. and Ciprut, S. and Bialik, S. and Berissi, H. and Albeck, S. and Peleg, Y. et al. 2011. GTP binding to the ROC domain of DAP-kinase regulates its function through intramolecular signalling. EMBO Reports. 12 (9): pp. 917-923.
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EMBO Reports
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School of Biomedical Sciences
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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. © 2011 European Molecular Biology Organization.