ROLE OF BETA-GAMMA-SUBUNITS OF G-PROTEINS IN TARGETING THE BETA-ADRENERGIC-RECEPTOR KINASE TO MEMBRANE-BOUND RECEPTORS
ROLE OF BETA-GAMMA-SUBUNITS OF G-PROTEINS IN TARGETING THE BETA-ADRENERGIC-RECEPTOR KINASE TO MEMBRANE-BOUND RECEPTORS
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DOI：
10.1126/science.1325672
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发表时间：
1992-08-28
期刊：
影响因子：
56.9
通讯作者：
LEFKOWITZ, RJ
中科院分区：
文献类型：
--
作者：
PITCHER, JA;INGLESE, J;LEFKOWITZ, RJ
β-肾上腺素能受体激酶（β-ARK）对β-2-肾上腺素能受体和视紫红质的激动剂依赖性磷酸化的速率和程度在加入G蛋白β-γ亚基后显著增强。用模型肽底物证明，激酶的直接活化不能解释这种效应。G蛋白β-γ亚基被证明直接与β-ARK的COOH-末端区域相互作用，并且这种β-ARK-β-γ复合物的形成导致酶的受体促进的膜定位。transducin的β-γ亚基在增强受体磷酸化速率和结合β-ARK的COOH-末端方面效果较差，表明该酶优先结合特异性β-γ复合物。β-ARK的β-γ介导的膜定位用于将受体活化与β-ARK介导的脱敏密切联系起来。
The rate and extent of the agonist-dependent phosphorylation of beta-2-adrenergic receptors and rhodopsin by beta-adrenergic receptor kinase (beta-ARK) are markedly enhanced on addition of G protein beta-gamma subunits. With a model peptide substrate it was demonstrated that direct activation of the kinase could not account for this effect. G protein beta-gamma subunits were shown to interact directly with the COOH-terminal region of beta-ARK, and formation of this beta-ARK-beta-gamma complex resulted in receptor-facilitated membrane localization of the enzyme. The beta-gamma subunits of transducin were less effective at both enhancing the rate of receptor phosphorylation and binding to the COOH-terminus of beta-ARK, suggesting that the enzyme preferentially binds specific beta-gamma complexes. The beta-gamma-mediated membrane localization of beta-ARK serves to intimately link receptor activation to beta-ARK-mediated desensitization.