Force-induced apoptosis mediated by the Rac/Pak/38 signalling pathway is regulated by filamin A

作者：Shifrin Yulia; Pinto Vanessa I; Hass****i Abbas; Arora Pamma D; McCulloch Christopher A^*

来源：Biochemical Journal, 2012, 445: 57-67.

DOI：10.1042/BJ20112119

• apoptosis
• filamin A
• mechanical force
• p21-activated kinase 1 (Pak1)
• p38 mitogen-activated protein kinase (p38 MAPK)
• Rac
• small GTPase

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 beta 1-integrins. Apoptosis was mediated by Rae-dependent activation of p38 alpha. 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 p38 alpha. We conclude that, in response to tensile force, filamin A regulates Rac-dependent signals, which induce apoptosis through Pak1 and p38.

• 出版日期2012-7-1