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首页> 外文期刊>Molecular and Cellular Biology >Protein Tyrosine Phosphatase α Phosphotyrosyl-789 Binds BCAR3 To Position Cas for Activation at Integrin-Mediated Focal Adhesions
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Protein Tyrosine Phosphatase α Phosphotyrosyl-789 Binds BCAR3 To Position Cas for Activation at Integrin-Mediated Focal Adhesions

机译:蛋白酪氨酸磷酸酶α磷酸酪氨酰-789结合BCAR3定位cas,以在整合素介导的粘着斑处活化

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Integrin-mediated focal adhesions connect the extracellular matrix and cytoskeleton to regulate cell responses, such as migration. Protein tyrosine phosphatase α (PTPα) regulates integrin signaling, focal adhesion formation, and migration, but its roles in these events are incompletely understood. The integrin-proximal action of PTPα activates Src family kinases, and subsequent phosphorylation of PTPα at Tyr789 acts in an unknown manner to promote migration. PTPα-null cells were used in reconstitution assays to distinguish PTPα-Tyr789-dependent signaling events. This showed that PTPα-Tyr789 regulates the localization of PTPα and the scaffolding protein Cas to adhesion sites where Cas interacts with and is phosphorylated by Src to initiate Cas signaling. Linking these events, we identify BCAR3 as a molecular connector of PTPα and Cas, with phospho-Tyr789 PTPα serving as the first defined cellular ligand for the BCAR3 SH2 domain that recruits BCAR3-Cas to adhesions. Our findings reveal a novel role of PTPα in integrin-induced adhesion assembly that enables Src-mediated activation of the pivotal function of Cas in migration.
机译:整联蛋白介导的粘着连接将细胞外基质和细胞骨架连接起来,以调节细胞反应,例如迁移。蛋白酪氨酸磷酸酶α(PTPα)调节整联蛋白信号传导,粘着斑形成和迁移,但其在这些事件中的作用尚不完全清楚。 PTPα的整联蛋白近端作用激活了Src家族激酶,随后Tyr789处PTPα的磷酸化以未知方式起作用,以促进迁移。 PTPα-null细胞用于重组测定,以区分PTPα-Tyr789依赖性信号事件。这表明PTPα-Tyr789调节PTPα和支架蛋白Cas的定位,使Cas与Cas相互作用并被Src磷酸化以启动Cas信号传导。链接这些事件,我们将BCAR3鉴定为PTPα和Cas的分子连接体,磷酸Tyr789PTPα充当BCAR3 SH2域的第一个定义的细胞配体,该结构使BCAR3-Cas募集到粘连。我们的发现揭示了PTPα在整联蛋白诱导的粘附装配中的新作用,该作用使Src介导的Cas的关键功能在迁移中激活。

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