The WASP-Binding protein WIRE has a role in the regulation of the actin filament system downstream of the platelet-derived growth factor receptor
The WASP-Binding protein WIRE has a role in the regulation of the actin filament system downstream of the platelet-derived growth factor receptor
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DOI：
10.1006/excr.2002.5576
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发表时间：
2002-09-10
影响因子：
3.7
通讯作者：
Aspenström, P
中科院分区：
文献类型：
--
作者：
Aspenström, P
生长因子受体的激活，如血小板衍生生长因子（PDGF）受体，对脊椎动物细胞的运动行为有重要影响。WASP家族蛋白通过激活Arp2/3复合物被认为是肌动蛋白聚合的重要调节因子。反过来，WASP蛋白的活性被证明是由一些相关蛋白控制的，包括WASP相互作用蛋白（WIP）。本文报道了一种新的wip样蛋白WIRE （WIP-related）。WIRE与WH1结合。WASP和N-WASP的结构域。在瞬时转染的PAE/PDGFRbeta细胞中，WIRE被定位到肌动蛋白丝上，在同时表达WIRE和WASP的细胞中，WIRE将WASP重新定位到肌动蛋白丝上，这种重新定位需要两种蛋白之间的直接相互作用。此外，WIRE还能结合PDGF受体底物Nckbeta。PDGF处理异位表达WIRE的细胞可形成由丝状足和片状足样结构组成的外周突起。在同时表达WIRE和WASP的细胞中，PDGF处理诱导WASP易位到细胞边缘，这一作用需要WIRE的存在。综上所述，这些数据表明WIRE在wasp介导的肌动蛋白细胞骨架组织中起作用，并且WIRE是激活的PDGF受体和肌动蛋白聚合机制之间的潜在联系。(C) 2002 Elsevier Science （USA）。
Activation of growth factor receptors, such as platelet-derived growth factor (PDGF) receptors, has a major impact on the motile behavior of vertebrate cells. The WASP family of proteins has been recognized as important regulators of actin polymerization via the activation of the Arp2/3 complex. The activity of the WASP proteins has, in turn, been shown to be governed by a number of associated proteins, including the WASP interacting protein (WIP). This report presents a novel WIP-like protein, WIRE (for WIP-related). WIRE was shown to bind to the WH1. domain of WASP and N-WASP. WIRE was localized to actin filaments in transiently transfected PAE/PDGFRbeta cells, and in cells simultaneously expressing WIRE and WASP, WIRE relocalized WASP to actin filaments, a relocalization that required direct interaction between the two proteins. In addition, WIRE was able to bind the PDGF receptor substrate Nckbeta. PDGF treatment of cells ectopically expressing WIRE resulted in formation of peripheral protrusions composed of filopodia and lamellipodia-like structures. In cells expressing both WIRE and WASP, PDGF treatment induced a translocation of WASP to the cell margin, an effect that required the presence of WIRE. Taken together, the data presented indicate that WIRE has a role in the WASP-mediated organization of the actin cytoskeleton and that WIRE is a potential link between the activated PDGF receptor and the actin polymerization machinery. (C) 2002 Elsevier Science (USA).