Ras-specific gtpase-activating proteins—structures, mechanisms, and interactions

K Scheffzek, G Shivalingaiah - Cold Spring …, 2019 - perspectivesinmedicine.cshlp.org
K Scheffzek, G Shivalingaiah
Cold Spring Harbor Perspectives in Medicine, 2019perspectivesinmedicine.cshlp.org
Ras-specific GTPase-activating proteins (RasGAPs) down-regulate the biological activity of
Ras proteins by accelerating their intrinsic rate of GTP hydrolysis, basically by a transition
state stabilizing mechanism. Oncogenic Ras is commonly not sensitive to RasGAPs caused
by interference of mutants with the electronic or steric requirements of the transition state,
resulting in up-regulation of activated Ras in respective cells. RasGAPs are modular
proteins containing a helical catalytic RasGAP module surrounded by smaller domains that …
Ras-specific GTPase-activating proteins (RasGAPs) down-regulate the biological activity of Ras proteins by accelerating their intrinsic rate of GTP hydrolysis, basically by a transition state stabilizing mechanism. Oncogenic Ras is commonly not sensitive to RasGAPs caused by interference of mutants with the electronic or steric requirements of the transition state, resulting in up-regulation of activated Ras in respective cells. RasGAPs are modular proteins containing a helical catalytic RasGAP module surrounded by smaller domains that are frequently involved in the subcellular localization or contributing to regulatory features of their host proteins. In this review, we summarize current knowledge about RasGAP structure, mechanism, regulation, and dual-substrate specificity and discuss in some detail neurofibromin, one of the most important negative Ras regulators in cellular growth control and neuronal function.
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