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α3β1 integrin promotes cell survival via multiple interactions between 14-3-3 isoforms and proapoptotic proteins
Cited 26 time in
Web of Science
Cited 27 time in Scopus
- Authors
- Issue Date
- 2009-11
- Publisher
- Elsevier
- Citation
- EXPERIMENTAL CELL RESEARCH 315 (2009) 3187-3200
- Keywords
- Laminin-5 ; PPFLMLLKGSTR motif ; Keratinocyte survival ; Anti-apoptosis ; 14-3-3ζ/p-Bad complex ; 14-3-3σ/p-YAP complex
- Abstract
- Laminin-5 and α3β1 integrin promote keratinocyte survival; however, the downstream signaling pathways for laminin-5/α3β1 integrin-mediated cell survival had not been fully established. We report the unexpected finding of multiple interactions between 14-3-3 isoforms and proapoptotic proteins in the survival signaling pathway. Ln5-P4 motif within human laminin-5 α3 chain promotes cell survival and anti-apoptosis by inactivating Bad and YAP. This effect is achieved through the formation of 14-3-3ζ/p-Bad and 14-3-3σ/p-YAP complexes, which is initiated by α3β1 integrin and FAK/PI3K/Akt signaling. These complexes result in cytoplasmic sequestration of Bad and YAP and their subsequent inactivation. An increase in Akt1 activity in cells induces 14-3-3ζ and σ, p-Bad, and p-YAP, promoting cell survival, whereas decreasing Akt activity suppresses the same proteins and inhibits cell survival. Suppression of 14-3-3ζ with RNA-interference inhibits cell viability and promotes apoptosis. These results reveal a new mechanism of cell survival whereby the formation of 14-3-3ζ/p-Bad and 14-3-3σ/p-YAP complexes is initiated by laminin-5 stimulation via the α3β1 integrin and FAK/PI3K/Akt signaling pathways, thereby resulting in cell survival and anti-apoptosis.
- ISSN
- 0014-4827
- Language
- English
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