Control of ras activation.
Ras proteins are active when bound to GTP and inactive when bound to GDP: the activation state of Ras proteins is regulated by two families of proteins. GTPase activating proteins (p120GAP, neurofibromin and GAP1) are negative regulators that stimulate hydrolysis of bound GTP to GDP, and guanine nucleotide exchange factors (Sos and Ras-GRF) are positive regulators that stimulate the exchange of GDP bound to Ras for fresh GTP from the cytosol. Ras is activated in response to a wide variety of extracellular stimuli. The principal mechanism used involves formation of complexes of autophosphorylated growth factor receptors with the SH2 and SH3 domain containing adaptor protein GRB2 and the exchange factor Sos. In addition, another adaptor protein, Shc, may bind to GRB2. This causes translocation of Sos to the plasma membrane where Ras is located and hence increases the rate of nucleotide exchange on Ras leading to its activation. The activity of GTPase activating proteins may also be regulated under some circumstances. A number of mechanisms exist to return the activation state of Ras to basal after stimulation.
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Imperial Cancer Research Fund, London.
D000818:Animals; D004789:Enzyme Activation; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D025542:Neurofibromin 1; D011506:Proteins; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins; D020663:ras Guanine Nucleotide Exchange Factors; D020666:ras-GRF1
D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D025542:Neurofibromin 1; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D020663:ras Guanine Nucleotide Exchange Factors; D020666:ras-GRF1; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)