Activation and attenuation of adenylate cyclase. The role of GTP-binding proteins as macromolecular messengers in receptor--cyclase coupling.
Activation and attenuation of adenylate cyclase. The role of GTP-binding proteins as macromolecular messengers in receptor--cyclase coupling.
复制标题
腺苷酸环化酶的激活和减弱。
作者：
L. Limbird
自从发现环AMP介导大量和多种激素的作用以来（Sutherland & Robison, 1966），人们对试图理解激素占据特定细胞表面受体导致膜结合腺苷酸环化酶激活的分子机制非常感兴趣，腺苷酸环化酶负责从ATP合成环AMP。尽管腺苷酸环化酶系统的最早概念表明激素可能通过在催化部分的变构位点结合来调节腺苷酸环化酶的活性，但最近已经证明腺苷酸环化酶系统由可分离的受体和催化亚基组成(Orly & Schramm, 1976; Limbird & Lefkowitz, 1977；Haga等人，1977a)，此外，还有第三种可分离成分，它赋予鸟嘌呤核苷酸对腺苷酸环化酶系统的多重调节作用（关于独立成分的生化特性的综述，请参阅Ross & Gilman， 1980）。本综述的重点是鸟嘌呤核苷酸的这些调节作用，以及越来越多的证据表明鸟嘌呤核苷酸调节蛋白（g蛋白）可能是激素占据受体和腺苷酸环化酶之间的功能性通讯器。这篇综述的视角是历史的；它试图总结关键的观察，确立了鸟嘌呤核苷酸在调节腺苷酸环化酶活性中的重要作用，并描述如何进一步的探索
Since the discovery that cyclic AMP mediates the action of a large number and variety of hormones (Sutherland & Robison, 1966), there has been considerable interest in trying to understand the molecular mechanisms by which hormone occupancy of specific cell surface receptors results in activation of membrane-bound adenylate cyclase, the enzyme responsible for synthesis of cyclic AMP from ATP. Although the earliest concepts of the adenylate cyclase system suggested that hormones might regulate adenylate cyclase activity via binding at allosteric sites on the catalytic moiety, more recently it has been demonstrated that adenylate cyclase systems consist of separable receptor and catalytic subunits (Orly & Schramm, 1976; Limbird & Lefkowitz, 1977; Haga et al., 1977a) and, in addition, a third separable component which confers the multiple regulatory effects of guanine nucleotides on the adenylate cyclase system (for a review focusing on the biochemical properties of the separate components see Ross & Gilman, 1980). The focus of the present review is on these regulatory effects of guanine nucleotides and on the growing body of evidence suggesting that the guanine nucleotide regulatory protein (G-protein) may represent the functional communicator between hormone-occupied receptors and the adenylate cyclase enzyme. The perspective of this review is a historical one; it attempts to summarize the critical observations that established the important role of guanine nucleotides in regulating adenylate cyclase activity and to describe how the further exploration