PARG1, a protein-tyrosine phosphatase-associated RhoGAP, as a putative Rap2 effector
PARG1, a protein-tyrosine phosphatase-associated RhoGAP, as a putative Rap2 effector
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DOI：
10.1016/j.bbrc.2005.02.069
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发表时间：
2005-04-15
影响因子：
3.1
通讯作者：
Kariya, K
中科院分区：
文献类型：
--
作者：
Myagmar, BE;Umikawa, M;Kariya, K
Rap2属于小gtp结合蛋白Ras家族，但其具体的信号作用尚不清楚。通过酵母双杂交筛选，我们发现与Rap2同源的线虫线虫与含有rho - gtpase激活蛋白（RhoGAP）结构域的蛋白ZK669.1a相互作用，其人类同源物PARG1在体外表现出RhoGAP活性。ZK669.1a和PARG1有一个同源区，功能未知，称为ZK669.1a和PARG1同源（ZPH）区。在这里，我们发现PARG1的ZPH区域介导与Rap2的相互作用。PARG1以依赖gtp的方式与Rap2相互作用，但不与Ras或Rap1相互作用。我们还发现，PARG1及其缺乏ZPH区域的突变体在成纤维细胞中诱导典型的Rho失活的细胞骨架变化。Rap2抑制了PARG1在体内的这种作用，但没有抑制突变体PARG1的作用。这些结果表明，PARG1可能是Rap2调控Rho的特异性效应体。(c) 2005爱思唯尔公司版权所有。
Rap2 belongs to the Ras family of small GTP-binding proteins, but its specific signaling role is unclear. By yeast two-hybrid screening, we have found that the Caenorhabditis elegans ortholog of Rap2 interacts with a protein containing a Rho-GTPase-activating protein (RhoGAP) domain, ZK669.1a, whose human ortholog PARG1 exhibits RhoGAP activity in vitro. ZK669.1a and PARG1 share a homology region with previously unknown function, designated the ZK669.1a and PARG1 homology (ZPH) region. Here we show that the ZPH region of PARG1 mediates interaction with Rap2. PARG1 interacted with Rap2 in a GTP-dependent manner but not with Ras or Rap1. We also show that PARG1 and its mutant lacking the ZPH region induce typical cytoskeletal changes for Rho inactivation in fibroblasts. Rap2 suppressed this in vivo action of PARG1 but not that of the mutant PARG1. These results suggest that PARG1 is a putative specific effector of Rap2 to regulate Rho. (c) 2005 Elsevier Inc. All rights reserved.