Regulation of Small GTPases by GEFs, GAPs, and GDIs

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作者：

J Cherfils，M Zeghouf

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摘要：

Small GTPases use GDP/alternation to actuate a variety of functional switches that are pivotal for cell dynamics. The GTPase switch is turned on by , which stimulate dissociation of the tightly bound GDP, and turned off by , which accelerate the intrinsically sluggish hydrolysis of . For , , and Rab GTPases, this switch incorporates a /alternation regulated by and -like proteins. The structures and core mechanisms of representative members of small GTPase regulators from most families have now been elucidated, illuminating their general traits combined with scores of unique features. Recent studies reveal that small GTPase regulators have themselves unexpectedly sophisticated regulatory mechanisms, by which they process cellular signals and build up specific cell responses. These mechanisms include multilayered autoinhibition with stepwise release, feedback loops mediated by the activated GTPase, feed-forward signaling flow between regulators and effectors, and a code for . The flipside of these highly integrated functions is that they make small GTPase regulators susceptible to biochemical abnormalities that are directly correlated with diseases, notably a striking number of missense mutations in , and susceptible to bacterial mimics of , , and that take command of small GTPases in . This review presents an overview of the current knowledge of these many facets of small GTPase regulation.

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关键词：

Allosteric Regulation Animals Catalytic Domain Enzyme Activation GTPase-Activating Proteins Guanine Nucleotide Dissociation Inhibitors Guanine Nucleotide Exchange Factors Guanosine Diphosphate Guanosine Triphosphate Humans