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
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.