Catalytic Domain of the p120 Ras GAP Binds to Rab5 and Stimulates Its GTPase Activity*
- Kebin Liu and
- Guangpu Li‡
- From the Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190
Abstract
Ras is a master GTPase switch controlling multiple signal transduction cascades in the regulation of cell proliferation and differentiation. Rab5 is a local GTPase switch that is localized on early endosomes and controls early endosome fusion. This study demonstrates that the catalytic domain of p120 GTPase-activating protein (GAP), a well known Ras GAP, is able to interact physically with Rab5 and stimulate its GTPase activity. This GAP activity toward Rab5, however, cannot be extended to other Rab GTPases such as Rab3, Rab4, and Rab6, indicating that it is not a generic GAP for the Rab family of GTPases that regulate intracellular membrane fusion during endocytosis and exocytosis. The findings indicate a level of structural similarity between Ras and Rab5 unexpected from their primary sequences. They also suggest a possible signal transduction regulation of the Rab5-dependent endosome fusion via the Ras GAP.
Footnotes
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↵* This work was supported in part by an Oklahoma Center for the Advancement of Science and Technology grant (to G. L.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed. Tel.: 405-271-2227 (ext. 1232); Fax: 405-271-3092; E-mail: guangpu-li{at}ouhsc.edu.
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↵1 The abbreviations used are: GAP, GTPase-activating protein; GAPette, the catalytic domain of the p120 GAP; GST, glutathione S-transferase; DTT, dithiothreitol; PAGE, polyacrylamide gel electrophoresis; GTPγS, guanosine 5′-O-(3-thiotriphosphate).
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- Received February 4, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
