Crosstalk between Gα i - and Gα q -coupled receptors is mediated by Gβγ exchange
- 14 September 1999
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 96 (19) , 10626-10631
- https://doi.org/10.1073/pnas.96.19.10626
Abstract
Activation of Galpha(i)-coupled receptors often causes enhancement of the inositol phosphate signal triggered by Galpha(q)-coupled receptors. To investigate the mechanism of this synergistic receptor crosstalk, we studied the Galpha(i)-coupled adenosine A(1) and alpha(2C) adrenergic receptors and the Galpha(q)-coupled bradykinin B(2) and a UTP-preferring P2Y receptor. Stimulation of either Galpha(i)-coupled receptor expressed in COS cells increased the potency and the efficacy of inositol phosphate production by bradykinin or UTP. Likewise, overexpression of Gbeta(1)gamma(2) resulted in a similar increase in potency and efficacy of bradykinin or UTP. In contrast, these stimuli did not affect the potency of direct activators of Galpha(q); a truncated Gbeta(3) mutant had no effect on the receptor-generated signals whereas signals generated at the G-protein level were still enhanced. This suggests that the Gbetagamma-mediated signal enhancement occurs at the receptor level. Almost all possible combinations of Gbeta(1-3) with Ggamma(2-7) were equally effective in enhancing the signals of the B(2) and a UTP-preferring P2Y receptor, indicating a very broad specificity of this synergism. The enhancement of the bradykinin signal by (i) Galpha(i)-activating receptor ligands or (ii) cotransfection of Gbetagamma was suppressed when the B(2) receptor was replaced by a B(2)Gbeta(2) fusion protein. Gbetagamma enhanced the B(2) receptor-stimulated activation of G-proteins as determined by GTPgammaS-induced decrease in high affinity agonist binding and by B(2) receptor-enhanced [(35)S]GTPgammaS binding. These findings support the concept that Gbetagamma exchange between Galpha(i)- and Galpha(q)-coupled receptors mediates this type of receptor crosstalk.Keywords
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