A FAMILY OF RECEPTORS COUPLED TO GUANINE-NUCLEOTIDE REGULATORY PROTEINS

A FAMILY OF RECEPTORS COUPLED TO GUANINE-NUCLEOTIDE REGULATORY PROTEINS
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DOI:
10.1021/bi00384a001
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发表时间:
1987-05-19
期刊:
影响因子:
2.9
通讯作者:
LEFKOWITZ, RJ
LEFKOWITZ, RJ
中科院分区:
生物学3区
文献类型:
--
作者:
DOHLMAN, HG;CARON, MG;LEFKOWITZ, RJ

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(将外部刺激转化为细胞内信号的细胞系统是细胞质膜的重要组成部分。一个新兴的范例是,这样的“跨膜信号系统”通常包括三个不同的组成部分。首先,有暴露在细胞膜外表面的特定受体,它们识别并与激素或药物等配体相互作用,或对光等感官刺激做出反应。第二,暴露在细胞质表面的是效应酶,如腺苷环化酶,它产生第二信使cAMP(Lefkowitz等人,1983)。效应酶还包括磷脂酶C(PLC)(将磷脂酰肌醇4,5-二磷酸水解成1,4,5-三磷酸肌醇和1,2-二酰基甘油)(Taylor&Merritt,1986)以及cGMP磷酸二酯酶(Klein,1984)。其他效应器可以作为离子通道(Pfaffinger等人,1985;Breitwiesser&Szabo,1985)。第三,许多受体和效应分子之间的物理和功能上都是转导或偶联蛋白,它们与GTP结合并水解物。这些是鸟嘌呤核苷酸调节蛋白,或“G蛋白”(Gilman,1984)。最近的证据表明,这种类型的信号系统显示出一定程度的结构、功能和调控上的同源性,这是以前没有意识到的。
(Cellular systems for the transduction of external stimuli into intracellular signals are essential components of the cellular plasma membrane. An emerging paradigm is that such “transmembrane signaling systems” often involve three distinct components. First, there are the specific receptors exposed at the external surface of the cell membrane that recognize and interactwith ligands such as hormones or drugs or respond to sensory stimuli such as light. Second, exposed at the cy-toplasmic surface are effector enzymes such as adenylate cyclase, which generates the second messenger cAMP (Lefkowitz et al., 1983). Effector enzymes also include phospholipase C (PLC)(whichhydrolyzes phosphatidylinositol 4, 5-bisphosphate to inositol 1, 4, 5-trisphosphate and 1, 2-di-acylglycerol)(Taylor & Merritt, 1986) as well as cGMP phosphodiesterase (Klein, 1984). Other effectors may act as ion channels (Pfaffinger et al., 1985; Breitwiesser & Szabo, 1985). Third, interposed physically and functionally between many receptor and effector molecules are transducing or coupling proteins, which bind and hydrolyze GTP. These are the guanine nucleotide regulatory proteins, or “G proteins”(Gilman, 1984). Recent evidence indicates that signaling systems of this type demonstrate a degree of structural, functional, and regulatory homologythat had not previously been appreciated.