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A human protein selected for interference with Ras function interacts directly with Ras and competes with Raf1.

机译:选择用于干扰Ras功能的人类蛋白质直接与Ras相互作用并与Raf1竞争。

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The overexpression of some human proteins can cause interference with the Ras signal transduction pathway in the yeast Saccharomyces cerevisiae. The functional block is located at the level of the effector itself, since these proteins do not suppress activating mutations further downstream in the same pathway. We now demonstrate, with in vivo and in vitro experiments, that the protein encoded by one human cDNA (clone 99) can interact directly with yeast Ras2p and with human H-Ras protein, and we have named this gene rin1 (Ras interaction/interference). The interaction between Ras and Rin1 is enhanced when Ras is bound to GTP. Rin1 is not able to interact with either an effector mutant or a dominant negative mutant of H-Ras. Thus, Rin1 displays a human H-Ras interaction profile that is the same as that seen for Raf1 and yeast adenylyl cyclase, two known effectors of Ras. Moreover, Raf1 directly competes with Rin1 for binding to H-Ras in vitro. Unlike Raf1, however, the Rin1 protein resides primarily at the plasma membrane, where H-Ras is localized. These data are consistent with Rin1 functioning in mammalian cells as an effector or regulator of H-Ras.
机译:某些人类蛋白质的过表达可能会干扰啤酒酵母中的Ras信号转导途径。功能块位于效应子本身的水平,因为这些蛋白不会抑制同一途径中下游的激活突变。现在,我们通过体内和体外实验证明,一个人cDNA(克隆99)编码的蛋白可以直接与酵母Ras2p和人H-Ras蛋白相互作用,并且我们将该基因命名为rin1(Ras相互作用/干扰) )。当Ras绑定到GTP时,Ras和Rin1之间的交互作用会增强。 Rin1不能与H-Ras的效应突变体或显性负突变体相互作用。因此,Rin1显示的人类H-Ras相互作用谱与Ras1和酵母腺苷酸环化酶(Ras的两个已知效应子)相同。此外,Raf1直接与Rin1竞争在体外与H-Ras的结合。但是,与Raf1不同,Rin1蛋白主要驻留在质膜上,质膜位于H-Ras。这些数据与Rin1在哺乳动物细胞中作为H-Ras的效应子或调节子发挥作用相一致。

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