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 GAP1m, GAP1IP4BP, CAPRI (Ca2+-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.
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Conference Article|
October 25 2006
The GAP1 family of GTPase-activating proteins: spatial and temporal regulators of small GTPase signalling
S. Yarwood;
S. Yarwood
1The Henry Wellcome Integrated Signalling Laboratories, Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, U.K.
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D. Bouyoucef-Cherchalli;
D. Bouyoucef-Cherchalli
1The Henry Wellcome Integrated Signalling Laboratories, Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, U.K.
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P.J. Cullen;
P.J. Cullen
1
1The Henry Wellcome Integrated Signalling Laboratories, Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, U.K.
1To whom correspondence should be addressed (email Pete.Cullen@bris.ac.uk).
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S. Kupzig
S. Kupzig
1The Henry Wellcome Integrated Signalling Laboratories, Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, U.K.
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Publisher: Portland Press Ltd
Received:
July 06 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (5): 846–850.
Article history
Received:
July 06 2006
Citation
S. Yarwood, D. Bouyoucef-Cherchalli, P.J. Cullen, S. Kupzig; The GAP1 family of GTPase-activating proteins: spatial and temporal regulators of small GTPase signalling. Biochem Soc Trans 1 October 2006; 34 (5): 846–850. doi: https://doi.org/10.1042/BST0340846
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