[Frontiers in Bioscience 3, d769-780, August 1, 1998]
Reprints
PubMed
CAVEAT LECTOR




Table of Conents
 Previous Section   Next Section

G-PROTEIN COUPLED RECEPTORS IN BONE

Wayne B. Bowler1, James A. Gallagher and Graeme Bilbe2

1 Human Bone Cell Research Group, Department of Human Anatomy and Cell Biology, University of Liverpool, England, L69 3GE 2 Novartis Pharma A.G., Postfach, K681.4.43, CH-4002 Basel, Switzerland

Received 1/16/98 Accepted 2/17/98

4. HETEROTRIMERIC G-PROTEINS P>G-proteins are composed of three subunits (alpha, beta and the smaller gamma subunits). The alpha subunit shares homology with the GTPase family, possesses intrinsic GTPase activity and contains sites for myristoylation and palmitoylation (reviewed in (12)). All gamma subunits contain sites for isoprenylation (reviewed in (12)). These acetylations target G-proteins to the membrane compartment, the principal site for G-protein signaling. P>Four G protein subfamilies have been identified and classified according to the known 23 alpha subunits (Gq/11, Gi/0 Gs and G12/13; (26)). There is a similar variety of beta (5) and gamma (11) subunits which are classed according to association with alpha subunits (19). These G protein subfamilies can be either stimulatory (Gq/11, Gi/0) or stimulatory and inhibitory (Gs). Furthermore, due to the host of interactions between alpha, beta and gamma subunits, many heterotrimeric species can be formed which confer increased specificity or flexibility of signaling. P>The mechanism by which G-proteins convert receptor/ligand interaction to effector activation has been reviewed extensively elsewhere (23, 84). Briefly, ligand binding results in a conformational change in the receptor cytoplasmic domain that promotes association with an inactive GDP-bound heterotrimeric G-protein. This interaction enhances dissociation of GDP from the receptor/G-protein complex, facilitating GTP binding, alpha subunit activation, and dissociation from the receptor. Dissociation of G-protein from the receptor results in alpha subunit dissociation, facilitating its interaction with effector molecules. Intrinsic alpha subunit GTPase activity catalyses GTP hydrolysis causing inactivation, a process often enhanced or activated by effector binding. GDP-bound alpha subunit re-associates with beta and gamma subunits to form an inactive G protein heterotrimer which is once again capable of interacting with the recepto

r.