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首页> 外文期刊>Molecular and Cellular Biology >Semaphorin 4D/Plexin-B1 Induces Endothelial Cell Migration through the Activation of PYK2, Src, and the Phosphatidylinositol 3-Kinase-Akt Pathway
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Semaphorin 4D/Plexin-B1 Induces Endothelial Cell Migration through the Activation of PYK2, Src, and the Phosphatidylinositol 3-Kinase-Akt Pathway

机译：Semaphorin 4D / Plexin-B1通过激活PYK2，Src和磷脂酰肌醇3-激酶-Akt途径诱导内皮细胞迁移。

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摘要

Semaphorins are cell surface and secreted proteins that provide axonal guidance in neuronal tissues and regulate cell motility in many cell types. They act by binding a family of transmembrane receptors known as plexins, which belong to the c-Met family of scatter factor receptors but lack an intrinsic tyrosine kinase domain. Interestingly, we have recently shown that Plexin-B1 is highly expressed in endothelial cells and that its activation by Semaphorin 4D elicits a potent proangiogenic response (J. R. Basile, A. Barac, T. Zhu, K. L. Guan, and J. S. Gutkind, Cancer Res. >64:5212-5224, 2004). In searches for the underlying molecular mechanism, we observed that Semaphorin 4D-stimulated endothelial cell migration requires the activation of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. Surprisingly, we found that Plexin-B1 stimulates PI3K-Akt through the activation of an intracellular tyrosine kinase cascade that involves the sequential activation of PYK2 and Src. This results in the tyrosine phosphorylation of Plexin-B1, the rapid recruitment of a multimeric signaling complex that includes PYK2, Src, and PI3K to Plexin-B1 and the activation of Akt. These findings suggest that Plexin-B1 may achieve its numerous physiological functions through the direct activation of intracellular tyrosine kinase cascades.
机译：信号量是细胞表面和分泌的蛋白，可在神经元组织中提供轴突指导并调节许多细胞类型中的细胞运动。它们通过结合称为plexins的跨膜受体家族起作用，该家族属于散射因子受体c-Met家族，但缺乏内在的酪氨酸激酶结构域。有趣的是，我们最近发现Plexin-B1在内皮细胞中高度表达，并且其被Semaphorin 4D激活会引起有效的促血管生成反应（JR Basile，A.Barac，T.Zhu，KL Guan和JS Gutkind，Cancer Res。 > 64： 5212-5224，2004）。在寻找潜在的分子机制时，我们观察到信号蛋白4D刺激的内皮细胞迁移需要激活磷脂酰肌醇3激酶（PI3K）-Akt途径。令人惊讶地，我们发现Plexin-B1通过细胞内酪氨酸激酶级联反应的激活来刺激PI3K-Akt，该级联反应涉及PYK2和Src的顺序激活。这导致Plexin-B1的酪氨酸磷酸化，包括PYK2，Src和PI3K的多聚信号复合物迅速募集到Plexin-B1并激活Akt。这些发现表明，Plexin-B1可通过直接激活细胞内酪氨酸激酶级联反应来实现其多种生理功能。

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