The GAP1 family of GTPase-activating proteins: spatial and temporal regulators of small GTPase signalling. (25th October 2006)

• Record Type: Journal Article
• Authors: Yarwood, S.; Bouyoucef-Cherchalli, D.; Cullen, P.J.; Kupzig, S.
• Is Part Of: Biochemical Society transactions. Volume 34:Number 5(2006)
• Page Start: 846
• Page End: 850
• Publication Date: 2006-10-25
• Subjects: Ca2+-promoted Ras inactivator (CAPRI) -- GTPase-activating protein 1 (GAP1) -- pleckstrin homology domain (PH domain) -- Ras -- Ras-GTPase-activating-like protein (RASAL) -- small GTPase; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST0340846
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : Ras proteins are binary switches that, by cycling between inactive GDP-bound and active GTP-bound conformations, regulate multiple cellular signalling pathways including those that control cell growth, differentiation and survival. Approximately 30% of all human tumours express Ras-containing oncogenic mutations that lock the protein into a constitutively active conformation. The activation status of Ras is regulated by two groups of proteins: GEFs (guanine nucleotide-exchange factors) bind to Ras and enhance the exchange of GDP for GTP, thereby activating it, whereas GAPs (GTPase-activating proteins) inactivate Ras by binding to the GTP-bound form and enhancing the hydrolysis of the bound nucleotide back to GDP. In this review, we focus on a group of key regulators of Ras inactivation, the GAP1 family of Ras-GAPs. The members of this family are GAP1 m, GAP1 IP4BP, CAPRI (Ca 2+ -promoted Ras inactivator) and RASAL (Ras-GTPase-activating-like protein) and, as we will discuss, they are emerging as important modulators of Ras and small GTPase signalling that are subject to regulation by a diverse array of events and second messenger signals.