Coordinating Speed and Amplitude in G-Protein Signaling

G-protein-mediated signaling is intrinsically kinetic. Signal output at steady state is a balance of the rates of GTP binding, which causes activation, and of GTP hydrolysis, which terminates activation. This GTPase catalytic cycle is regulated by receptors, which accelerate GTP binding, and GTPase-activating proteins (GAPs), which accelerate hydrolysis. Receptors and GAPs similarly control the rates of signal initiation and termination. To allow independent control of signal amplitude and of the rates of turning the signal on and off, the activities of receptors and GAPs must be coordinated. Here, the principles of such coordination and the mechanisms by which it is achieved are discussed.