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首页> 外文期刊>EMBO Journal >Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold
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Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold

机译:疤痕/第一波,Wiskott-Aldrich综合症蛋白质,组装一个actin-associated multi-kinase脚手架

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摘要

WAVE proteins are members of the Wiskott-Aldrich syndrome protein (WASP) family of scaffolding proteins that coordinate actin reorganization by coupling Rho-related small molecular weight GTPases to the mobilization of the Arp2/3 complex. We identified WAVE-1 in a screen for rat brain A kinase-anchoring proteins (AKAPs), which bind to the SH3 domain of the Abelson tyrosine kinase (Abl). Recombinant WAVE-1 interacts with cAMP-dependent protein kinase (PKA) and Abl kinases when expressed in HEK-293 cells, and both enzymes co-purify with endogenous WAVE from brain extracts. Mapping studies have defined binding sites for each kinase. Competition experiments suggest that the PKA-WAVE-1 interaction may be regulated by actin as the kinase binds to a site overlapping a verprolin homology region, which has been shown to interact with actin. Immunocytochemical analyses in Swiss 3T3 fibroblasts suggest that the WAVE-1 kinase scaffold is assembled dynamically as WAVE, PKA and Abl translocate to sites of actin reorganization in response to platelet-derived growth factor treatment, Thus, we propose a previously unrecognized function for WAVE-1 as an actin-associated scaffolding protein that recruits PKA and Abl. [References: 46]
机译:波蛋白质Wiskott-Aldrich的成员综合征蛋白(黄蜂)脚手架的家庭协调肌动蛋白重组蛋白质耦合Rho-related小分子量gtpase Arp2/3的动员复杂。大脑kinase-anchoring蛋白(akap)绑定到SH3 Abelson酪氨酸的域激酶(Abl)。cAMP-dependent蛋白激酶(PKA)和机载激光器激酶表达在hek - 293细胞,两者兼而有之从大脑与内源酶co-purify波提取物。网站为每个激酶。表明PKA-WAVE-1交互由肌动蛋白激酶绑定到一个网站重叠verprolin同源区域,已被证明与肌动蛋白进行交互。采用免疫分析在瑞士3 t3成纤维细胞表明第一波激酶支架组装动态波,PKA和肌动蛋白的Abl把网站重组对血小板源的反应生长因子治疗,因此,我们提出一个以前未被认识的第一波作为一个函数actin-associated支架蛋白,新兵PKA, Abl。

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