title: 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.
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors: Rodrigo
authors: R
authors: Carlessi
authors: Vered
authors: V
authors: Levin-Salomon
authors: Sara
authors: S
authors: Ciprut
authors: Shani
authors: S
authors: Bialik
authors: Hanna
authors: H
authors: Berissi
authors: Shira
authors: S
authors: Albeck
authors: Yoav
authors: Y
authors: Peleg
authors: Adi
authors: A
authors: Kimchi
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D064550:Death-Associated Protein Kinases; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D055503:Protein Multimerization; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins; D006160:Guanosine Triphosphate; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D015689:Oncogene Protein p21(ras)