Regulators of G-protein signalling: a novel protein family involved in timely deactivation and desensitization of signalling via heterotrimeric G proteins.
In a variety of signalling pathways heterotrimeric guanine-nucleotide-binding proteins (G proteins) trigger physiological responses elicited by hormones, neurotransmitters and sensory stimuli. Receptor-induced GDP/GTP exchange activates G proteins by dissociating G-protein alpha-subunits from the betagamma-dimers. Both alpha-subunits and betagamma-dimers are involved in effector regulation. The deactivation of these active forms is controlled by the hydrolysis of GTP bound to alpha-subunits, allowing the inactive heterotrimer to reform. Termination of G-protein-mediated signalling in vivo is 10- to 100-fold faster than the in vitro rate of GTP hydrolysis by alpha-subunits, suggesting that in analogy to the GTPases of the Ras-superfamily, GTPase-activating proteins (GAPs) are required to achieve timely deactivation. Recently, members of a novel protein superfamily, known as "regulators of G-protein signalling" (RGS), were identified as potent GAPs for at least one subset of heterotrimeric G-protein alpha-subunits. In this review, we intend to discuss the proposed mechanism by which RGS proteins exert GAP activity for G-protein alpha-subunits as well as their specificities. The role of RGS proteins in desensitization and temporal resolution in certain signalling pathways will also be addressed.
Wieland
T
T
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany. wieland@uke.uni-hamburg.de
Chen
C K
CK
D000818:Animals; D020558:GTP Phosphohydrolases / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D020690:GTPase-Activating Proteins; D006801:Humans; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D020703:ras GTPase-Activating Proteins; D018631:ras Proteins / Q000502:physiology
D020690:GTPase-Activating Proteins; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D018631:ras Proteins