GUANINE NUCLEOTIDE BINDING PROTEIN BETA-GAMMA DIMERS--STRUCTURE AND FUNCTION

鸟嘌呤核苷酸结合调节蛋白（G蛋白）是 作为跨膜信号转导子的A1 B1 G1异源三聚体 通过将细胞外刺激的受体与细胞内刺激的受体偶联， 效应器（酶、离子通道）。 G蛋白构成了一种多样的 以特异性受体和效应物相互作用为特征的家族 而这又取决于三个组成部分的结构 亚单位。 a亚基结合鸟嘌呤核苷酸， 在效应器调节中的作用。 B和g亚基是 作为BG复合物紧密结合，包含单个功能性 像a亚基一样，是G蛋白绝对需要的实体 与受体的相互作用。 bg的效应调节作用 复杂性在一些系统中变得越来越明显。 的 目前的研究强调BG复合物在 G蛋白介导的信号转导。在这一年里， Gb 5同种型以及一系列Gb 1的功能特性 在瞬时转染的COS中研究卷曲螺旋点突变体 细胞 据了解，结构上不同的Gb 5同种型，而 有能力调节PLC-b信号传导，不能激活 ERK 2/MAPK或JNK信号传导与Gb 1一样级联。 此外，我们还发现， Gb 1中的D20 K点突变促进JNK而不是PLC-b 信号装置. 综合这些发现， Gbg调节各种效应靶点的机制在不同的 效应器 研究结果还表明，Gbg螺旋线圈在 JNK激活机制 这些研究可能有助于阐明 BG亚单位复合物调节结构的机制 根据激动剂刺激的不同效应分子。

The guanine-nucleotide binding regulatory proteins (G-proteins) are a1b1g1 heterotrimers which function as transmembrane signal transducers by coupling receptors for extracellular stimuli to intracellular effectors (enzymes, ion channels). G-proteins constitute a diverse family distinguished by specific receptor and effector interactions which in turn are determined by the structure of the three constituent subunits. The a subunit binds guanine nucleotides and has a well established role in effector modulation. The b and g subunits are tightly associated as a bg complex, comprising a single functional entity which, like the a subunit, is absolutely required for G-protein interaction with receptor. An effector modulatory role for the bg complex is becoming increasingly apparent in several systems. The present research emphasizes the role of the bg complex in G-protein-mediated signal transduction. During this year the effector functional properties of the Gb5 isoform as well as a series of Gb1 coiled-coil point mutants were studied in transiently transfected COS cells. It was learned that the structurally distinct Gb5 isoform, while competent to regulate PLC-b signalling, was not able to activate the ERK2/MAPK or JNK signalling cascades as Gb1 could. In addition we found that a D20K point mutation in Gb1 facilitated JNK but not PLC-b signalling. Taken together these findings suggest that the mechanism by which Gbg modulates various effector targets differs among the effectors. The findings also implicate the Gbg coiled-coil in the mechanism of JNK activation. These studies may help elucidate the mechanism(s) by which the bg subunit complex modulates structurally diverse effector molecules pursuant to agonist stimulation.