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- Title
Force-induced apoptosis mediated by the Rac/Pak/p38 signalling pathway is regulated by filamin A.
- Authors
SHIFRIN, Yulia; PINTO, Vanessa I.; HASSANALI, Abbas; ARORA, Pamma D.; MCCULLOCH, Christopher A.
- Abstract
Cells in mechanically challenged environments cope with highamplitude 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 ß1-integrins. Apoptosis was mediated by Rac-dependent activation of p38a. 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 p38a. We conclude that, in response to tensile force, filamin A regulates Rac-dependent signals, which induce apoptosis through Pak1 and p38.
- Subjects
APOPTOSIS; FILAMINS; GTPASE-activating protein; FORCE &; energy; CELLULAR signal transduction; CELLULAR mechanics; CELL death
- Publication
Biochemical Journal, 2012, Vol 445, Issue 1, p57
- ISSN
0264-6021
- Publication type
Article
- DOI
10.1042/BJ20112119