Class II phosphatidylinositol 3-kinases (PI3K), PI3K-C2α and PI3K-C2β, are involved in cellular processes including endocytosis, cilia formation and autophagy. However, the role of PI3K-C2α and PI3K-C2β at the organismal level is not well understood. We found that double knockout (KO) mice with both smooth muscle-specific KO of PI3K-C2α and global PI3K-C2β KO, but not single KO mice of either PI3K-C2α or PI3K-C2β, exhibited reductions in arterial blood pressure and substantial attenuation of contractile responses of isolated aortic rings. In wild-type vascular smooth muscle cells, double knockdown of PI3K-C2α and PI3K-C2β but not single knockdown of either PI3K markedly inhibited contraction with reduced phosphorylation of 20-kDa myosin light chain and MYPT1 and Rho activation, but without inhibition of the intracellular Ca²⁺ mobilization. These data indicate that PI3K-C2α and PI3K-C2β play the redundant but essential role for vascular smooth muscle contraction and blood pressure regulation mainly through their involvement in Rho activation.

中文翻译：

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小鼠血管平滑肌Rho活化，收缩和血压调节需要II类磷脂酰肌醇3-激酶α和β亚型

II类磷脂酰肌醇3-激酶（PI3K），PI3K-C2α和PI3K-C2β参与细胞过程，包括内吞，纤毛形成和自噬。然而，关于PI3K-C2α和PI3K-C2β在机体水平上的作用尚不清楚。我们发现同时具有PI3K-C2α和整体PI3K-C2βKO平滑肌特异性KO的双敲除（KO）小鼠，但没有PI3K-C2α或PI3K-C2β的单只KO小鼠表现出动脉血压降低和实质性降低减弱孤立的主动脉环的收缩反应。在野生型血管平滑肌细胞中，PI3K-C2α和PI3K-C2β的双重敲除可显着抑制收缩，同时降低20kDa肌球蛋白轻链的磷酸化以及MYPT1和Rho的活化，但不抑制PI3K-C2α和PI3K-C2β的单一敲除。细胞内钙²⁺动员。这些数据表明PI3K-C2α和PI3K-C2β主要通过参与Rho活化而在血管平滑肌收缩和血压调节中起着多余但必不可少的作用。