GTP-binding Proteins as Cellular Signal Transducer

这项名为“GTP结合蛋白作为细胞信号转导蛋白”的研究项目得到了优先领域科学研究补助金的支持，由两组组成，第一组研究主题如下：第一组研究α-异三聚体G蛋白的机制和作用；第二组研究低分子GTP结合蛋白的机制和作用。虽然这两大家族的GTP结合蛋白都在膜受体启动的细胞内信号网络中发挥着重要作用，但它们作为信号蛋白的功能却截然不同。前者偶联并介导所有由受体触发的细胞内信号，其共同的蛋白质结构具有特殊的七个跨膜螺旋结构域，其生理激动剂基本上包括所有的神经递质、神经肽和蛋白质激素(胰岛素除外)。后者在细胞内…中起着关键作用刺激生长因子(包括胰岛素)、细胞因子和其他类金丝桃体的受体，会产生更多的信号级联。这些受体在结构和功能上与异源三聚体G蛋白偶联受体明显不同；受体蛋白具有酪氨酸激酶结构域，或者，尽管没有内源性激酶活性，但在触发细胞内信号的第一步激活非受体类型的蛋白酪氨酸激酶。低分子GTP结合蛋白，如Ras、Rho.Rab和其他亚家族，最终将这些信号与细胞增殖、基因表达、形态变化、细胞间接触和细胞内蛋白运输联系起来。属于这两个项目的任何一个小组的所有研究人员都在这些国际竞争非常激烈的研究领域做出了自己的原创贡献。特别引人注目的贡献是该项目的首席调查员及其同事所作的贡献。他们提出了与PtdIns3-Kinase相关的新机制，来解释这两个不同信号系统之间的“串扰”。较少

This research project, entitled "GTP-binding Proteins as Cellular Signal Transducer" and supported by Grant-in-Aid for Scientific Research on Priority Areas, consisted of two groups with the following research subjects, i, e., the first group with "Mechanisms and Roles of alphabetagamma-Hetero-trimeric G-Proteins" ant the second group with "Mechanisms and Roles of Low-molecular GTP-binding proteins". Although both of these big families of GTP-binding proteins play essential roles in membrane receptor-initiated intracellular signaling network, their functions as signaling proteins are distinctly different from each other. The former is coupled to, and mediated all the intracellular signals triggered by, receptors whose common protein structure is characterized by particular seven membrane-spanning helical domains and whose physiological agonists include essentially all of neurotransmitters, neuropeptides and protein hormones (except insulin). The latter plays a pivotal role in intracell … More ular signaling cascades arising from stimulation of receptors for growth factors (including insulin), cytokines and other autacoids. These receptors are distinctly different from heterotrimeric G-protein-coupled receptors in structure and function ; the receptor proteins possess tyrosine kinase domains or, alternatively, though having no endogenous kinase activity, activate non-receptor-type protein tyrosine kinases at the first step of triggered intracellular signaling. The low-molecular GTP-binding proteins, such as Ras, Rho.Rab and other subfamilies, function to link these signaling eventually to cell proliferation, gene expression, morphological changes, cell-cell contact and intracellular protein traffics. All the investigators belonging to either of these two groups of the project have made their own original contributions in these internationally very competitive fields of research. Particularly striking contributions were those made by the head investigator of the project and his colleagues. They have proposed new mechanisms, related to PtdIns 3-kinase, of the "crosstalk" between these two different signaling systems. Less