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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Requirement of Nck adaptors for actin dynamics and cell migration stimulated by platelet-derived growth factor B
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Requirement of Nck adaptors for actin dynamics and cell migration stimulated by platelet-derived growth factor B

机译：Nck衔接子对血小板衍生生长因子B刺激的肌动蛋白动力学和细胞迁移的要求

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摘要

The Nck family of Src homology (SH) 2/SH3 domain adaptors functions to link tyrosine phosphorylation induced by extracellular signals with downstream regulators of actin dynamics. We investigated the role of mammalian Nck adaptors in signaling from the activated platelet-derived growth factor (PDGF) receptor (PDGF beta R) to the actin cytoskeleton. We report here that Nck adaptors are required for cytoskeletal reorganization and chemotaxis stimulated by PDGF-B. Analysis of tyrosine-phosphorylated proteins demonstrated that Crk-associated substrate (p130(Cas)), not the activated PDGF beta R itself, is the major Nck SH2 domain-binding protein in PDGF-B-stimulated cells. Both Nck- and p130(Cas)-deficient cells fail to display cytoskeletal rearrangements, including the formation of membrane ruffles and the disassembly of actin bundles, typically shown by their WT counterparts in response to PDGF-B. Furthermore, Nck and p130(Cas) colocalize in phosphotyrosine-enriched membrane ruffles induced by PDGF-B in NIH 3T3 cells. These results suggest that Nck adaptors play an essential role in linking the activated PDGF beta R with actin dynamics through a pathway that involves p130(Cas).
机译：Nck家族的Src同源性（SH）2 / SH3域适配器的功能是将胞外信号诱导的酪氨酸磷酸化与肌动蛋白动力学的下游调节子联系起来。我们研究了哺乳动物Nck衔接子在从活化的血小板衍生生长因子（PDGF）受体（PDGFβR）到肌动蛋白细胞骨架的信号传导中的作用。我们在这里报告，Nck适配器是PDGF-B刺激的细胞骨架重组和趋化性所必需的。酪氨酸磷酸化蛋白的分析表明，Crk相关的底物（p130（Cas）），而不是激活的PDGF beta R本身，是PDGF-B刺激的细胞中主要的Nck SH2结构域结合蛋白。缺乏Nck和p130（Cas）的细胞均无法显示细胞骨架重排，包括膜褶皱的形成和肌动蛋白束的分解，通常由其WT对应物对PDGF-B的反应所显示。此外，Nck和p130（Cas）在NIH 3T3细胞中由PDGF-B诱导的富含磷酸酪氨酸的膜褶中共定位。这些结果表明，Nck衔接子在通过涉及p130（Cas）的途径将活化的PDGF beta R与肌动蛋白动力学连接中起着至关重要的作用。

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