Roles for the tubulin- and PTP-PEST-binding paxillin LIM domains in cell adhesion and motility
Roles for the tubulin- and PTP-PEST-binding paxillin LIM domains in cell adhesion and motility
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DOI：
10.1016/s1357-2725(01)00154-6
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发表时间：
2002-07-01
影响因子：
4
通讯作者：
Turner, CE
中科院分区：
文献类型：
--
作者：
Brown, MC;Turner, CE
通过细胞-细胞外基质接触介导的细胞动力学，如粘附和运动性，涉及称为粘着斑（FA）的结构和信号分子的大复合物的精确调节。桩蛋白是一种多结构域FA衔接蛋白，含有5个氨基末端桩蛋白亮氨酸-天冬氨酸重复（LD）基序和4个羧基末端Lin-11 Isl-1和Mec-3（LIM）结构域。LD基序支持桩蛋白与actopaxin（整合素连接激酶（ILK））结合。FA激酶（FAK）。桩蛋白激酶接头（PKL）和黏着斑蛋白。在LIM结构域中，LIM 2和3包含桩蛋白FA靶向基序，这些结构域的磷酸化调节桩蛋白靶向和细胞粘附至纤连蛋白（Fn）。桩蛋白FA靶向伴侣的身份仍有待确定;然而，LIM结构域介导与微管蛋白和蛋白酪氨酸磷酸酶（PTP）-PEST的相互作用。PTP-PEST结合需要LIM 3和4两者，而微管蛋白结合的精确LIM靶标尚不清楚。在这份报告中。我们证明了单个桩蛋白LIM 2和3结构域支持与微管蛋白的特异性结合，并表明这种相互作用在桩蛋白亚细胞区室化的调节中具有潜在的作用。此外，在微管和PTP-PEST结合LIM结构域中具有突变的桩蛋白分子的表达差异性地损害中国仓鼠卵巢K I（CHOX I）细胞粘附和迁移至Fn。LIM 3或LIM 4的干扰抑制粘附，而LIM 2或LIM 4的突变降低细胞运动性。有趣的是，串联LIM 2 -3的表达抑制了细胞粘附和铺展，而LIM 3 -4刺激了良好铺展的极化表型。这些数据进一步支持桩蛋白在细胞粘附和运动中的关键作用。(C)2002爱思唯尔科技有限公司。保留所有权利。
Cell dynamics mediated through cell-extracellular matrix contacts, such as adhesion and motility involve the precise regulation of large complexes of structural and signaling molecules called focal adhesions (FAs), Paxillin is a multi-domain FA adaptor protein containing five amino-terminal paxillin leucine-aspartate repeat (LD) motifs and four carboxyl-terminal Lin-11 Isl-1 and Mec-3 (LIM) domains. The LD motifs support paxillin binding to actopaxin, integrin linked kinase (ILK). FA kinase (FAK). paxillin kinase linker (PKL) and vinculin. Of the LIM domains, LIM2 and 3 comprise the paxillin FA-targeting motif, with phosphorylation of these domains modulating paxillin targeting and cell adhesion to fibronectin (Fn). The identity of the paxillin FA targeting partner remains to be determined; however, the LIM domains mediate interactions with tubulin and the protein-tyrosine phosphatase (PTP)-PEST. PTP-PEST binding requires both LIM3 and 4, whereas, the precise LIM target of tubulin binding is not known. In this report. we demonstrate that the indiVidUal paxillin LIM2 and 3 domains,, support specific binding to tubulin and suggest a potential role for this interaction in the regulation of paxillin sub-cellular compartmentalization. In addition, express,ion of paxillin molecules with Mutations in the tubuling and PTP-PEST-binding LIM domains differentially impaired Chinese hamster ovary K I (CHOX I) cell adhesion and migration to Fn. Perturbation of LIM3 or 4 inhibited adhesion while mutation of LIM2 or 4 decreased cell motility. Interestingly, expression of tandem LIM2-3 inhibited cell adhesion and spreading while LIM3-4 Stimulated a well-spread polarized phenotype. These data offer further support for a critical role for paxillin in cell adhesion and motility. (C) 2002 Elsevier Science Ltd. All rights reserved.