The small G-proteins KRas, HRas, and NRas function as GDP–GTP regulated binary switches in many signal transduction pathways that govern cell growth and differentiation. Alternation between the GDP-bound ‘off’ state and the GTP-bound ‘on’ state is controlled by the guanine nucleotide exchange factors (GEFs) SOS1 and SOS2, which catalyze the exchange of GDP for GTP, and by GTPase-activating proteins (GAPs), which terminate the ‘on’ state by catalyzing the hydrolysis of GTP to GDP (Fig. 1).
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