Protein kinase C induces actin reorganization via a Src- and Rho-dependent pathway
Protein kinase C induces actin reorganization via a Src- and Rho-dependent pathway
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DOI：
10.1074/jbc.m200946200
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发表时间：
2002-06-07
影响因子：
4.8
通讯作者：
Mischak, H
中科院分区：
文献类型：
--
作者：
Brandt, D;Gimona, M;Mischak, H
我们研究了pkc诱导A7r5血管平滑肌细胞中肌动蛋白重组的机制。PKC被12- o -十四烷酰基磷酸-13-醋酸酯激活后，肌动蛋白应激纤维的分解伴随着膜褶的出现。PKC还在这些细胞中诱导快速酪氨酸磷酸化。正如我们所示，利用sre特异性抑制剂PP2和激酶缺陷的c-Sre突变体，肌动蛋白重组依赖于pkc诱导的Src激活。随后，小g蛋白RhoA活性降低，而Rac和Cdc42活性保持不变。使用Rho激酶特异性抑制剂Y-27632也可以观察到肌动蛋白应力纤维的分解，这表明RhoA活性的降低本身就是肌动蛋白重组的原因。此外，我们发现p190RhoGAP的酪氨酸磷酸化在12- o -十四烷酰基磷酸-13-乙酸刺激下增加，直接将Src激活与RhoA活性降低联系起来。我们的数据为阐明pkc诱导的肌动蛋白重排的分子机制的模型提供了大量证据。
We have investigated the mechanism of PKC-induced actin reorganization in A7r5 vascular smooth muscle cells. PKC activation by 12-O-tetradecanoylphorbol-13-acetate induces the disassembly of actin stress fibers concomitant with the appearance of membrane ruffles. PKC also induces rapid tyrosine phosphorylation in these cells. As we could show, utilizing the Sre-specific inhibitor PP2 and a kinase-deficient c-Sre mutant, actin reorganization is dependent on PKC-induced Src activation. Subsequently, the activity of the small G-protein RhoA is decreased, whereas Rac and Cdc42 activities remain unchanged. Disassembly of actin stress fibers could also be observed using the Rho kinase-specific inhibitor Y-27632, indicating that the decrease in RhoA activity on its own is responsible for actin reorganization. In addition, we show that tyrosine phosphorylation of p190RhoGAP is increased upon 12-O-tetradecanoylphorbol-13-acetate stimulation, directly linking Src activation to a decrease in RhoA activity. Our data provide substantial evidence for a model elucidating the molecular mechanisms of PKC-induced actin rearrangements.