Regulation of mammalian adenylyl cyclases by G-protein alpha and beta gamma subunits.
Regulation of mammalian adenylyl cyclases by G-protein alpha and beta gamma subunits.
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G 蛋白 α 和 β γ 亚基对哺乳动物腺苷酸环化酶的调节。
DOI：
10.1101/sqb.1992.057.01.017
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Gilman,AG
中科院分区：
文献类型：
--
作者：
Tang,WJ;Iñiguez-Lluhi,JA;Mumby,S;Gilman,AG
异源三聚体鸟嘌呤核苷酸结合调节蛋白（G蛋白）家族的成员负责将信息从许多膜结合受体传递至其细胞内效应物（综述参见Gilman 1987; Kaziro et al.1991; Simon et al.1991）。有几种这样的途径;研究得最好的是用于cAMP合成速率的双重（刺激和抑制）调节（例如，通过β-肾上腺素能和毒蕈碱激动剂）和用于视网膜杆和锥中cGMP的光刺激水解的途径。现在认识到，已经阐明的腺苷酸环化酶和视觉系统的信号转导途径的一般特征--信息从细胞外定向受体流向G蛋白再流向细胞内效应物--被大量跨膜信号传导系统所共享，这些跨膜信号传导系统由激素、神经递质、autacoids、气味剂或物理刺激触发。由G蛋白控制的生理事件的范围（从机制上讲）从G蛋白与效应子直接相互作用已得到结论性证明的事件，到G蛋白明显参与但机制不确定的事件，再到G蛋白控制的事件。蛋白可能但未经证实。G蛋白和效应子之间的直接相互作用已被证明分别通过Gs、G（transducin）和Gq/Gll的et亚基刺激调节腺苷酸环化酶（Northup et al.1983; May et al.1985）、视网膜cGMP特异性磷酸二酯酶（Stryer 1986）和磷脂酶C-131（Smrcka et al.1991; Taylor et al.1991）。有明确的证据表明G蛋白参与腺苷酸环化酶的抑制性调节（Katada等人，1984），骨骼肌和心肌中电压敏感性Ca++通道活性的调节（Brown和Birnbaumer 1988）和神经元（Hescheler et al.1987），以及心房肌细胞（Yatani et al.1987，1988）、神经元（货车Dongen et al.1988）和其他地方（Brown and Birnbaumer 1990）中K δ通道的门控。然而，在这些情况下，机制仍有待确定。虽然已经证明了不涉及低分子量第二信使的途径，但尚不清楚G蛋白效应器相互作用是否是直接的，或者是否有其他大分子组分作为所涉及的G蛋白的主要靶点。最后，还有一些G蛋白，其作用相当模糊（例如，G12，G13 [Strathmann和Simon 1991]），
Members of a family of heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) are responsible for transmission of information from many membrane-bound receptors to their intracellular effectors (for reviews, see Gilman 1987; Kaziro et al. 1991; Simon et al. 1991). There are several such pathways; the best-studied are those for dual (stimulatory and inhibitory) regulation of the rate of cAMP synthesis (eg, by/3-adrenergic and muscarinic agonists) and for light-stimulated hydrolysis of cGMP in retinal rods and cones. It is now appreciated that the general features of signal transduction pathways that have been elucidated for adenylyl cyclases and the visual system--that information flows from extracellularly oriented receptor to G protein to intracellular effector--are shared by a large number of transmembrane signaling systems that are triggered by hormones, neurotransmitters, autacoids, odorants, or physical stimuli. Physiological events that are controlled by G proteins range (mechanistically) from those in which the direct interaction of G protein with effector has been demonstrated conclusively, to those in which a G protein is clearly involved but the mechanism is uncertain, to those in which control by a G protein is likely but unproven. Direct interactions between G proteins and effectors have been demonstrated for stimulatory regulation of adenylyl cyclase (Northup et al. 1983; May et al. 1985), retinal cGMP-specific phosphodiesterase (Stryer 1986), and phospholipase C-131 (Smrcka et al. 1991; Taylor et al. 1991) by the et subunits of Gs, G,(transducin), and Gq/Gll, respectively. There is clear evidence for the involvement of G proteins in the inhibitory regulation of adenylyl cyclase (Katada et al. 1984), the modulation of activity of voltage-sensitive Ca++ channels in skeletal and cardiac muscle (Brown and Birnbaumer 1988) and neurons (Hescheler et al. 1987), and the gating of K § channels in atrial muscle cells (Yatani et al. 1987, 1988), neurons (Van Dongen et al. 1988), and elsewhere (Brown and Birnbaumer 1990). However, in these cases, mechanisms remain to be determined. Although pathways that do not involve low-molecular-weight second messengers have been demonstrated, it is not yet known if the G proteineffector interaction is direct or if there are other macromolecular components that serve as primary targets for the G proteins involved. Finally, there are G proteins whose roles are reasonably obscure (eg, G12, G13 [Strathmann and Simon 1991]), pathways where