Although many proteins bind GTP (e.g. actin, tubulin) the GTP-binding proteins are considered special cases because of their role in signalling. There are two classes of these G proteins: heterotrimeric G proteins that associate with G-protein-coupled receptors, and the small cytoplasmic G proteins. The heterotrimeric G proteins have a Gα subunit (39–52 kDa) with slow GTP-ase activity: when GTP binds the α subunit dissociates from the βγ subunits (β, 35–36 kDa: γ, 6–10 kDa) and is able to interact with various second messenger systems, either inhibiting (Gi), stimulating (Gs), or otherwise (Go). Once the GTP is hydrolysed the heterotrimer re-forms and activation ceases. The βγ subunits, most of which are membrane associated through post-translational myristoylation or isoprenylation, may have direct activating effects in their own right, though they are less diverse than the α subunits. Stimulatory G proteins (Gαs-βγ) are permanently activated by cholera toxin, inhibitory ones (Gαi-βγ) by pertussis toxin. Transducin (Gαt-βγ) was one of the first of the heterotrimeric G proteins to be identified. The small G proteins are a diverse group of monomeric GTPases that include ras, rab, rac, and rho and play an important part in regulating many intracellular processes including cytoskeletal organization and secretion. Their GTPase activity is regulated by activators (GTPase-activating protein, GAPs) and inhibitors (GIPs) that determine the duration of the active (GTP-bound) state. See also GEFs; ras-like GTPases.
Subjects: Medicine and Health.