Cellular expression of the carboxyl terminus of a G protein-coupled receptor kinase attenuates G beta gamma-mediated signaling.
Cellular expression of the carboxyl terminus of a G protein-coupled receptor kinase attenuates G beta gamma-mediated signaling.
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DOI：
10.1016/s0021-9258(17)37587-7
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发表时间：
1994-02
期刊：
影响因子：
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通讯作者：
W. Koch;B. Hawes;James Inglese;L. Luttrell;R. Lefkowitz
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文献类型：
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作者：
W. Koch;B. Hawes;James Inglese;L. Luttrell;R. Lefkowitz
异源三聚体G蛋白的β-伽马亚基(G-β-γ)调节包括G蛋白偶联受体激酶在内的几个信号转导效应分子的活性。G-β-γ与β-肾上腺素能受体激酶(β-ARK)的羧基末端结合并调节其活性。为了研究这种Gβ结合结构域对异源Gβ伽马相互作用的影响，在COS-7细胞中与βARK1的羧基末端共表达了多种能够刺激磷脂酶C和/或II型腺苷环化酶的受体。共表达的β-ARK1多肽能显著抑制通过Giβ-γ受体(α2-肾上腺素能和M2-M胆碱能受体)刺激磷脂酶C的磷酸肌醇水解酶，而Gqα亚基(α1-肾上腺素能和M 1-M M能受体)对磷酸肌醇的催化作用不受影响。由于受体和共表达的腺苷环化酶II的刺激而导致的细胞内cAMP水平升高，在存在βARK1多肽的情况下表现出明显的抑制作用。此外，对刺激α2-肾上腺素能受体产生的腺苷环化酶(GIα介导的过程)的抑制没有影响，表明βARK1多肽为区分Gα和Gβ伽马通路提供了一个有用的工具。
The beta gamma subunits (G beta gamma) of heterotrimeric G proteins modulate the activity of several signal-transducing effector molecules including G protein-coupled receptor kinases. G beta gamma binds to the carboxyl terminus of the beta-adrenergic receptor kinase (beta ARK) and regulates its activity. To investigate the effect of such a G beta gamma-binding domain on heterologous G beta gamma interactions, various receptors that can stimulate phospholipase C and/or type II adenylate cyclase were coexpressed in COS-7 cells with the carboxyl terminus of beta ARK1. Phosphoinositol hydrolysis in response to activation of receptors that stimulate phospholipase C via Gi beta gamma (alpha 2-adrenergic and M2-muscarinic cholinergic receptors) was markedly inhibited by the coexpressed beta ARK1 polypeptide, whereas that mediated by Gq alpha subunits (alpha 1-adrenergic and M1-muscarinic cholinergic receptors) was unaffected. Increased cellular cAMP levels due to stimulation of receptors and coexpressed adenylate cyclase II displayed marked inhibition in the presence of the beta ARK1 polypeptide. Moreover, inhibition of adenylate cyclase produced by alpha 2-adrenergic receptor stimulation (a Gi alpha-mediated process) was unaffected, indicating that the beta ARK1 polypeptide provides a useful tool for distinguishing between G alpha and G beta gamma pathways.