The small monomeric and heterotrimeric G-proteins function as molecular switches that control a wide range of cellular pathways including signal transduction from receptor complexes at the inner plasma membrane, trafficking of internal vesicles, nuclear import, cell cycle progression, cytoskeletal reorganization, and protein translation. These switches cycle between an active conformation in which they bind GTP and an inactive GDP-bound form (Fig. 1). In the simplest model, they can only interact productively with downstream effectors when bound to GTP [1].

While all G-proteins can be viewed as inefficient GTPases, some are more inefficient than others. For example, Arf proteins have barely detectable intrinsic GTP hydrolysis, Ras proteins have kcat values of V0. 02/min, and GK subunits have kcat values of up to V 2.5/min [2]. One common feature of the G-proteins is that their rate of GTP hydrolysis is enhanced^ often dramatically^ by interacting with specióc GTPase activating proteins (GAPs)[3, 4]. Consequently, GAPs are important negative regulators of G-protein signaling. Somatic mutations of the genes encoding Ras and the K subunits of heterotrimeric G-proteins are found in human cancers [5, 6].