A human protein selected for interference with Ras function interacts directly with Ras and competes with Raf1.
A human protein selected for interference with Ras function interacts directly with Ras and competes with Raf1.
复制标题
选择干扰 Ras 功能的人类蛋白质直接与 Ras 相互作用并与 Raf1 竞争。
DOI：
10.1128/mcb.15.3.1318
复制
发表时间：
1995
影响因子：
5.3
通讯作者：
Colicelli,J
中科院分区：
文献类型：
--
作者：
Han,L;Colicelli,J
某些人源蛋白的过量表达可干扰酿酒酵母中Ras信号转导途径。功能块位于效应物本身的水平，因为这些蛋白质不抑制同一途径中更下游的激活突变。我们现在通过体内和体外实验证明，由一个人cDNA（克隆99）编码的蛋白质可以直接与酵母Ras 2 p和人H-Ras蛋白相互作用，我们将此基因命名为rin 1（Ras相互作用/干扰）。当Ras与GTP结合时，Ras和Rin 1之间的相互作用增强。Rin 1不能与H-Ras的效应突变体或显性负突变体相互作用。因此，Rin 1显示出与Raf 1和酵母腺苷酸环化酶（Ras的两种已知效应物）相同的人H-Ras相互作用谱。此外，Raf 1在体外直接与Rin 1竞争结合H-Ras。然而，与Raf 1不同的是，Rin 1蛋白主要位于质膜上，H-Ras位于质膜上。这些数据与Rin 1在哺乳动物细胞中作为H-Ras的效应子或调节子起作用一致。
The overexpression of some human proteins can cause interference with the Ras signal transduction pathway in the yeastSaccharomyces 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.