BRIDGING RAL GTPASE TO RHO-PATHWAYS - RLIP76, A RAL EFFECTOR WITH CDC42/RAC GTPASE-ACTIVATING PROTEIN ACTIVITY
BRIDGING RAL GTPASE TO RHO-PATHWAYS - RLIP76, A RAL EFFECTOR WITH CDC42/RAC GTPASE-ACTIVATING PROTEIN ACTIVITY
复制标题
DOI：
10.1074/jbc.270.38.22473
复制
发表时间：
1995-09-22
影响因子：
4.8
通讯作者：
CAMONIS, JH
中科院分区：
文献类型：
--
作者：
JULLIENFLORES, V;DORSEUIL, O;CAMONIS, JH
RalA和RalB是功能未知的GTP酶，由蛋白质RalGDS激活，RalGDS与另一种GTP酶的活性形式Pas相互作用。为了阐明RalA的功能，我们使用双杂交方法和Jurkat细胞库寻找与RalA的活化形式相互作用的蛋白质。我们已经确定了一个部分的cDNA编码的蛋白质，RLIP 1，它结合到激活的RalA，这种结合需要一个完整的效应结构域的RalA。纯化的RalA的生化数据证实了遗传结果。该蛋白质还具有与参与Rho家族的GTP酶的调节的GTP酶激活蛋白（GAP）结构域同源的区域，并且实际上，RLIP 1显示作用于Rad和CDC 42而不是RhoA的GAP活性。该GAP区域不是RLIP 1结合RalA所必需的。克隆了完整的cDNA，它编码一个76-kDa的多肽RLIP 76，该多肽也结合RalA。Rho通路参与有丝分裂刺激后细胞膜和细胞骨架的修饰，与Pas通路平行并协同作用。我们认为这些通路通过Pas -> RalGDS -> Rac 1-> RLIP 76-> CDC 42/Rac 1/Rho组成的级联连接，从而允许Pas通路调节Rho通路。
RalA and RalB are GTPases of unknown function and are activated by proteins, RalGDS, that interact with the active form of another GTPase, Pas. To elucidate Pal function, we have searched for proteins interacting with an activated-form of RalA using the two-hybrid method and a Jurkat cell library. We have identified a partial cDNA encoding a protein, RLIP1, which binds to activated RalA and this binding requires an intact effector domain of RalA. Biochemical data with purified RalA confirm the genetic results, This protein also bears a region of homology with GTPase-activating protein (GAP) domains that are involved in the regulation of GTPases of the Rho family and, indeed, RLIP1 displays a GAP activity acting upon Rad and CDC42, but not RhoA. This GAP region is not required for RLIP1 binding to Pal.The whole cDNA was cloned, and it encodes a 76-kDa polypeptide, RLIP76, which also binds RalA. The Rho pathway is involved in membrane and cytoskeleton modifications after mitogenic stimulation and acts in parallel to and synergistically with the Pas pathway, We propose that these pathways are linked through a cascade composed of Pas --> RalGDS --> Pal --> RLIP76 --> CDC42/Rac1/Rho, allowing modulation of the Rho pathway by the Pas pathway.