A MOLECULAR MECHANISM FOR SIGNALING BETWEEN 7-TRANSMEMBRANE RECEPTORS- EVIDENCE FOR A REDISTRIBUTION OF G-PROTEINS

Citation
Y. Djellas et al., A MOLECULAR MECHANISM FOR SIGNALING BETWEEN 7-TRANSMEMBRANE RECEPTORS- EVIDENCE FOR A REDISTRIBUTION OF G-PROTEINS, Proceedings of the National Academy of Sciences of the United Statesof America, 95(18), 1998, pp. 10944-10948
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary Sciences
ISSN journal
0027-8424
Volume
95
Issue
18
Year of publication
1998
Pages
10944 - 10948
Database
ISI
SICI code
0027-8424(1998)95:18<10944:AMMFSB>2.0.ZU;2-2
Abstract
Although activation of one seven-transmembrane receptor can influence the response of a separate seven-transmembrane receptor, e.g., the phe nomenon of synergism, the underlying mechanism(s) for this signaling p ro cess is unclear. The present study investigated communication betwe en two receptors that exhibit classical synergism, e.g., human platele t thrombin and thromboxane A(2) receptors. Activation of thrombin rece ptors caused an increase in ligand affinity of thromboxane A(2) recept ors. This effect (i) was shown to be specific, since a similar increas e in ligand affinity was not caused by ADP or A23187; (ii) did not req uire cytosolic components, e.g., kinases, proteases, phosphatases, etc ., because it occurred in isolated platelet membranes; (iii) was G pro tein-mediated because it was blocked by an G(alpha q) C terminus antib ody; and (iv) was associated with a net increase in G(alpha q) couplin g to thromboxane A(2) receptors. Collectively, these data provide evid ence that seven-transmembrane receptors that share a common G(alpha) s ubunit can communicate with each other via a redistribution of their G proteins. Thus, activation of thrombin receptors increases G(alpha q) association with thromboxane A(2) receptors thereby shifting them to a higher affinity state. This signaling phenomenon, which modulates re ceptor-ligand affinity, may serve as a molecular mechanism for cellula r adaptive processes such as synergism.