Crosstalk between Gαi- and Gαq-coupled receptors is mediated by Gβγ exchange

被引:75
作者
Quitterer, U [1 ]
Lohse, MJ [1 ]
机构
[1] Univ Wurzburg, Inst Pharmakol & Toxikol, D-97078 Wurzburg, Germany
关键词
D O I
10.1073/pnas.96.19.10626
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Activation of G alpha(i)-coupled receptors often causes enhancement of the inositol phosphate signal triggered by G alpha(q)-coupled receptors, To investigate the mechanism of this synergistic receptor crosstalk, we studied the G alpha(i)-coupled adenosine A(1) and alpha(2C) adrenergic receptors and the G alpha(q-)coupled bradykinin B-2 and a UTP-preferring P2Y receptor. Stimulation of either G alpha(i)-coupled receptor expressed in COS cells increased the potency and the efficacy of inositol phosphate production by bradykinin or UTP. Likewise, overexpression of G beta(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 G alpha(q); a truncated G beta(3) mutant had no effect on the receptor-generated signals whereas signals generated at the G-protein level mere still enhanced. This suggests that the G beta gamma-mediated signal enhancement occurs at the receptor level. Almost all possible combinations of G beta(1-3) with G gamma(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) G alpha(i)-activating receptor ligands or (ii) cotransfection of G beta gamma was suppressed when the B-2 receptor was replaced by a B(2)G beta(2) fusion protein. G beta gamma enhanced the B-2 receptor-stimulated activation of G-proteins as determined by GTP gamma S-induced decrease in high affinity agonist binding and by B-2 receptor-enhanced [S-35]GTP gamma S binding. These findings support the concept that G beta gamma exchange between G alpha(i)- and G alpha(q)-coupled receptors mediates this type of receptor crosstalk.
引用
收藏
页码:10626 / 10631
页数:6
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