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首页> 外文期刊>Molecular and Cellular Biology >Protein Kinase Cδ-Mediated Phosphorylation of Phospholipase D Controls Integrin-Mediated Cell Spreading
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Protein Kinase Cδ-Mediated Phosphorylation of Phospholipase D Controls Integrin-Mediated Cell Spreading

机译：蛋白激酶Cδ介导的磷脂酶D的磷酸化控制整合素介导的细胞扩散。

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Integrin signaling plays critical roles in cell adhesion, spreading, and migration, and it is generally accepted that to regulate these integrin functions accurately, localized actin remodeling is required. However, the molecular mechanisms that control the targeting of actin regulation molecules to the proper sites are unknown. We previously demonstrated that integrin-mediated cell spreading and migration on fibronectin are dependent on the localized activation of phospholipase D (PLD). However, the mechanism underlying PLD activation by integrin is largely unknown. Here we demonstrate that protein kinase Cδ (PKCδ) is required for integrin-mediated PLD signaling. After integrin stimulation, PKCδ is activated and translocated to the edges of lamellipodia, where it colocalizes with PLD2. The abrogation of PKCδ activity inhibited integrin-induced PLD activation and cell spreading. Finally, we show that Thr566 of PLD2 is directly phosphorylated by PKCδ and that PLD2 mutation in this region prevents PLD2 activation, PLD2 translocation to the edge of lamellipodia, Rac translocation, and cell spreading after integrin activation. Together, these results suggest that PKCδ is a primary regulator of integrin-mediated PLD activation via the direct phosphorylation of PLD, which is essential for directing integrin-induced cell spreading.
机译：整联蛋白信号传导在细胞粘附，扩散和迁移中起关键作用，并且普遍接受的是，要精确调节这些整联蛋白功能，需要局部肌动蛋白重塑。但是，控制肌动蛋白调节分子靶向适当位点的分子机制尚不清楚。我们先前证明整合素介导的细胞在纤连蛋白上的扩散和迁移取决于磷脂酶D（PLD）的局部活化。但是，整合素激活PLD的基本机制尚不清楚。在这里，我们证明整合素介导的PLD信号传导需要蛋白激酶Cδ（PKCδ）。整联蛋白刺激后，PKCδ被激活并易位到lamellipodia的边缘，在此处与PLD2共定位。 PKCδ活性的取消抑制了整合素诱导的PLD活化和细胞扩散。最后，我们显示PLD2的Thr566被PKCδ直接磷酸化，并且该区域中的PLD2突变阻止了PLD2激活，PLD2易位到lamellipodia的边缘，Rac易位以及整联蛋白激活后细胞扩散。在一起，这些结果表明PKCδ是通过PLD的直接磷酸化来整合素介导的PLD活化的主要调节剂，这对于指导整合素诱导的细胞扩散是必不可少的。

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