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GTP-binding Proteins as Cellular Signal Transducer

GTP 结合蛋白作为细胞信号转导器

基本信息

批准号：
05271101
负责人：
UI Michio
金额：
$ 75.07万
依托单位：
The Tokyo Metropolitan Institute of Medical Science (1995-1996)The Institute of Physical and Chemical Research (1993-1994)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1996
项目状态：
已结题

项目摘要

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

该研究项目名为“作为细胞信号传导器的GTP结合蛋白”，由优先领域科学研究资助金资助，由两个小组组成，研究主题如下，即，第一组为“α-γ-肝素-三聚体G蛋白的作用机制”，第二组为“低分子GTP结合蛋白的作用机制”。虽然这两个大家族的GTP结合蛋白在膜受体启动的细胞内信号网络中发挥重要作用，但它们作为信号蛋白的功能明显不同。前者与受体偶联并介导由受体触发的所有细胞内信号，受体的共同蛋白质结构的特征在于特定的七个跨膜螺旋结构域，并且其生理激动剂基本上包括所有神经递质、神经肽和蛋白质激素（胰岛素除外）。后者在细胞内起着关键作用 ...更多信息刺激生长因子（包括胰岛素）、细胞因子和其他自药受体引起的细胞信号级联。这些受体在结构和功能上明显不同于异源三聚体G蛋白偶联受体;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传导的第一步激活非受体型蛋白酪氨酸激酶。低分子量的GTP结合蛋白如Ras、Rho、Rab等亚家族，其功能是将这些信号最终与细胞增殖、基因表达、形态学变化、细胞间接触和细胞内蛋白质运输联系起来。所有属于这两个项目组的研究人员都在这些国际上极具竞争力的研究领域做出了自己的原创性贡献。特别引人注目的贡献是由该项目的首席研究员和他的同事。他们提出了与PtdIns 3-激酶相关的这两种不同信号系统之间的“串扰”的新机制。少