Department of Cellular Dynamics, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Cell Mol Life Sci. 2010 May;67(9):1547-57. doi: 10.1007/s00018-010-0267-0. Epub 2010 Jan 29.
Actin-directed processes such as membrane ruffling and cell migration are regulated by specific signal transduction pathways that become activated by growth factor receptors. The same signaling pathways that lead to modifications in actin dynamics also activate cPLA(2)alpha. Moreover, arachidonic acid, the product of cPLA(2)alpha activity, is involved in regulation of actin dynamics. Therefore, it was investigated whether cPLA(2)alpha plays a role in actin dynamics, more specifically during growth factor-induced membrane ruffling and cell migration. Upon stimulation of ruffling and cell migration by growth factors, endogenous cPLA(2)alpha and its active phosphorylated form were shown to relocate at protrusions of the cell membrane involved in actin and membrane dynamics. Inhibition of cPLA(2)alpha activity with specific inhibitors blocked growth factor-induced membrane and actin dynamics, suggesting an important role for cPLA(2)alpha in these processes.
肌动蛋白定向过程,如膜皱襞和细胞迁移,受到特定信号转导途径的调节,这些途径通过生长因子受体被激活。导致肌动蛋白动力学改变的相同信号通路也激活了 cPLA(2)alpha。此外,cPLA(2)alpha 活性产生的花生四烯酸参与肌动蛋白动力学的调节。因此,研究了 cPLA(2)alpha 是否在肌动蛋白动力学中发挥作用,更具体地说,在生长因子诱导的膜皱襞和细胞迁移过程中发挥作用。在生长因子刺激膜皱襞和细胞迁移时,内源性 cPLA(2)alpha 和其活性磷酸化形式被证明重新定位到参与肌动蛋白和膜动力学的细胞膜突起处。用特异性抑制剂抑制 cPLA(2)alpha 活性阻断了生长因子诱导的膜和肌动蛋白动力学,表明 cPLA(2)alpha 在这些过程中起着重要作用。