Promiscuity and fidelity in receptor-G-protein coupling: cell cycle-dependent coupling of the vasopressin V1 receptor.
Promiscuity and fidelity in receptor-G-protein coupling: cell cycle-dependent coupling of the vasopressin V1 receptor.
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受体-G-蛋白偶联的混杂性和保真度：加压素 V1 受体的细胞周期依赖性偶联。
DOI：
10.1042/bst0270158
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发表时间：
1999
影响因子：
3.9
通讯作者：
G. Schultz
中科院分区：
文献类型：
--
作者：
F. Kalkbrenner;A. Abel;N. Wittau;G. Schultz
细胞膜中的许多信号转导系统允许细胞对多种细胞外化学或物理刺激做出反应，如激素和感觉信号。一个重要的信号转导系统是由七次跨越质膜并利用异源三聚体GTP结合蛋白(G蛋白)来控制效应系统的受体所代表的，该效应系统进而控制细胞内离子和其他第二信使的浓度。G蛋白偶联受体(GPCRs)包括一个蛋白质超家族，到目前为止大约有。已对300名成员进行了功能描述(见[L-41])。其中许多受体是药物的重要靶点。除了鉴定的受体外，通过同源克隆已鉴定出2000多个可能编码GPCRs的基因。与大量的受体相比，只有有限的G蛋白可用。异源三聚体G蛋白由3个亚基组成，其中23个不同的α、5p和11y亚基(包括剪接变异体)已被克隆(见S-121)。由于GPCR信号转导级联的两个主要组成部分的数量不平衡，因此在受体与G蛋白的相互作用中是否存在重叠或透射性的问题出现了。更复杂的事实是：(1)单个激素与不同亚型的受体结合，(2)不同激素的受体可以偶联到同一G-蛋白池，(3)GPCRs和G-蛋白的组织特异性表达导致受体-G-蛋白偶联的组织特异性，以及(4)一个受体可以控制一个以上的效应系统。直到几年前，人们还认为
Many signal transduction systems in the membrane allow cells to respond to multiple extracellular chemical or physical stimuli, such as hormonal and sensory signals. One important signal transduction system is represented by receptors that span the plasma membrane seven times and utilize heterotrimeric GTP-binding proteins (G-proteins) to govern effector systems that in turn control intracellular concentrations of ions and other second messengers. The G-protein-coupled receptors (GPCRs) encompass a superfamily of proteins, of which until now approx. 300 members have been functionally characterized (reviewed in [l-41). Many of these receptors are important targets for drugs. In addition to the characterized receptors more than 2000 genes putatively encoding GPCRs have been identified by homology cloning. In contrast with the vast number of receptors, only a limited repertoire of G-proteins is available. Heterotrimeric G-proteins consist of three subunits, of which 23 (including splice variants) different a-, 5 p-and 11 y-subunits have been cloned (reviewed in [S-121). Because of this unbalanced number of the two major components of GPCR signal transduction cascades, the question arises whether there is an overlap or permissiveness in the interaction of receptors with G-proteins. This matter is even more complicated by the fact that (1) single hormones bind to different subtypes of receptors,(2) receptors for different hormones can couple to the same pool of G-proteins,(3) tissue-specific expression of GPCRs and G-proteins cause tissue specificity in receptor-G-protein coupling, and (4) one receptor can control more than one effector system. Until a few years ago, it was assumed that the