Force-induced apoptosis mediated by the Rac/Pak/p38 signalling pathway is regulated by filamin A.
Biochem J
; 445(1): 57-67, 2012 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-22489840
ABSTRACT
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 ß1-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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Apoptosis
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Proteínas Contráctiles
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Proteína de Unión al GTP rac1
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Mecanotransducción Celular
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Proteínas Quinasas p38 Activadas por Mitógenos
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Quinasas p21 Activadas
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Proteínas de Microfilamentos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Biochem J
Año:
2012
Tipo del documento:
Article