GTP Cycle

RAS-family proteins are low-molecular-weight guanine-nucleotide-binding proteins. They are inactive when bound to GDP and active when bound to GTP. Regulation of this molecular switch mechanism occurs through a GDP–GTP cycle that is controlled by the opposing activities of guanine nucleotide-exchange factors (GEFs), which catalyse the exchange of GDP for GTP, and GTPase-activating proteins (GAPs), which increase the rate of GTP hydrolysis to GDP (see diagram). In the case of RHO proteins, another layer of regulation is provided by RHO–GDP-dissociation inhibitors (RHOGDIs), which sequester RHO away from the GDP–GTP cycle. GTPases interact with various effector proteins, which influence the activity and/or localization of these effectors; this ultimately influences cell-cycle progression.