Force-induced apoptosis mediated by the Rac/Pak/p38 signalling pathway is regulated by filamin A.
Force-induced apoptosis mediated by the Rac/Pak/p38 signalling pathway is regulated by filamin A.
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DOI：
10.1042/bj20112119
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发表时间：
2012-07
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影响因子：
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通讯作者：
Y. Shifrin;Vanessa I. Pinto;A. Hassanali;P. D. Arora;C. McCulloch
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文献类型：
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作者：
Y. Shifrin;Vanessa I. Pinto;A. Hassanali;P. D. Arora;C. McCulloch
在机械挑战的环境中的细胞科普高振幅的外源性力量，可以导致细胞死亡，但介导力诱导的细胞凋亡和机械保护细胞因子的身份的机制没有定义。我们评估了暴露于通过β1-整合素施加的张力的NIH 3 T3和HEK（人胚肾）-293细胞中的凋亡。细胞凋亡是由Rac依赖的p38α激活介导的。消耗Pak 1（p21激活激酶1），下游效应的Rac，防止力诱导的p38激活和凋亡。细丝蛋白A可将Rac募集到力传递位点，抑制Rac和p38α介导的力诱导的细胞凋亡。我们的结论是，在响应张力，细丝蛋白A调节Rac依赖的信号，诱导细胞凋亡，通过Pak 1和p38。
Cells in mechanically challenged environments cope with high-amplitude exogenous forces that can lead to cell death, but the mechanisms that mediate force-induced apoptosis and the identity of mechanoprotective cellular factors are not defined. We assessed apoptosis in NIH 3T3 and HEK (human embryonic kidney)-293 cells exposed to tensile forces applied through β1-integrins. Apoptosis was mediated by Rac-dependent activation of p38α. Depletion of Pak1 (p21-activated kinase 1), a downstream effector of Rac, prevented force-induced p38 activation and apoptosis. Rac was recruited to sites of force transfer by filamin A, which inhibited force-induced apoptosis mediated by Rac and p38α. We conclude that, in response to tensile force, filamin A regulates Rac-dependent signals, which induce apoptosis through Pak1 and p38.