Signal transduction of Small GTP-binding proteins

有一个小的GTP结合蛋白（G蛋白）超家族，由60多个成员组成。所有成员都是具有20，000和30，000之间的Mrs的单体蛋白质，其表现出GDP/GTP结合和GTP酶活性。在本研究项目中，我们研究了小G蛋白的功能和激活和作用模式。Ras是该超家族的代表，并且众所周知至少通过由MAP激酶、MAP激酶（MEK）和MEK激酶组成的MAP激酶级联来调节基因表达。我们从牛脑中纯化了一种MEK激酶，该激酶在无细胞系统中以GTP γ S-Ki-Ras依赖的方式激活MEK，并将其鉴定为与14-3-3蛋白复合的B-Raf。我们还发现，Rapl，其具有相同的氨基酸序列在其效应域的Ras，也参与激活的B-Raf依赖的MAP激酶级联。Rho调节肌动蛋白丝的重组，并至少参与维持 ...更多信息 细胞形态学、细胞运动性和胞质分裂。我们发现，当细胞受到HGF和TPA刺激时，Rho可转位到细胞膜皱褶区，在胞质分裂时产生的收缩环上也可观察到Rho。ERM家族（Ezrin，Radixin和Moesin）通过其C-末端区域直接与肌动蛋白丝相互作用，并通过其N-末端区域与跨膜蛋白CD 44相互作用，位于这些区域。因此，Rho可以调节ERM家族依赖的肌动蛋白丝与质膜的关联的重组。我们还发现Rho GDI直接与ERM相互作用，通过降低Rho GDI活性来启动Rho的激活。Rho也存在于酿酒酵母中，并且我们发现Rho是芽殖过程所必需的。我们从遗传学和生物化学上分离了Rho的调控蛋白（RDI 1和ROM 1/ROM 2）和靶蛋白（PKC 1，BNI 1/BNR 1，葡聚糖合酶）。BNI 1和BNR 1直接与profilin在FH 1结构域相互作用，表明Rho通过BNI 1/BNR 1-profilin系统调节肌动蛋白丝的重组。Rab 3A是Rab家族的成员，其特别涉及从神经末梢释放神经递质。本研究还分离了Rab 3A、Rab 3 GEP和Rab 3 GAP的其他调控蛋白。少

There is the small GTP-binding protein (G protein) superfamily which consists of over sixty members. All the members are monomeric proteins with Mrs between 20,000 and 30,000 which exhibit both GDP/GTP-binding and GTPase activities. In the present research project, we studied the functions and modes of activation and action of small G proteins. Ras is the representative of this superfamily and is well known to regulate gene expression at least through the MAP kinase cascade consisting of MAP kinase, MAP kinase kinase (MEK), and MEK kinase. We purified from bovine brain a MEK kinase which activated MEK in a GTPgammaS-Ki-Ras-dependent manner in a cell-free system and identified it as B-Raf complexed with 14-3-3 proteins. We also found that Rapl, which has the same amino acid sequence at its effector domain as that of Ras, is also involved in the activation of the B-Raf-dependent MAP kinase cascade. Rho regulates reorganization of actin filaments and is implicated in at least maintenance … More of cell morphology, cell motility, and cytokinesis in mammalian cells. We found that Rho is translocated to a membrane ruffling area when cells are stimulated by HGF and TPA.Rho was also observed at the contractile ring produced during cytokinesis. The ERM family (Ezrin, Radixin, and Moesin), which directly interacts with actin filaments through its C-terminal region and with a transmembrane protein, CD44, through its N-terminal region, is located at these areas. Therefore, Rho may regulate reorganization of the ERM family-dependent association of actin filaments with the plasma membrane. We also found that Rho GDI directly interacts with ERM,initiating the activation of Rho by reducing the Rho GDI activity. Rho also exists in the yeast Saccharomyces cerevisiae, and we found that Rho is essential for budding process. We genetically and biochemically isolated the regulatory proteins (RDI1 and ROM1/ROM2) and target proteins (PKC1, BNI1/BNR1, glucan synthase) for Rho. BNI1 and BNR1 directly interact with profilin at the FH1 domains, suggesting that Rho regulates the reorganization of actin filaments through the BNI1/BNR1-profilin system. Rab3A is a member of the Rab family which is particularly implicated in neurotransmitter release from the nerve terminal. We had isolated its regulatory protein, named Rab GDI,and its target protein, named Rabphilin-3A.In this research project, we isolated other regulatory proteins for Rab3A,Rab3 GEP and Rab3 GAP. Less