[alpha]3[beta]1 integrin promotes cell survival via multiple interactions between 14-3-3 isoforms and proapoptotic proteins

• Published in: Experimental cell research 2009-11, Vol.315 (18), p.3187
• Main Authors: Oh, Ju-Eun, Jang, Da Hyun, Kim, Hyunsoo, Kang, Hyun Ki, Chung, Chong-Pyoung, Park, Won Ho, Min, Byung-Moo
• Format: Article
• Language: English
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2009.08.002

Laminin-5 and [alpha]3[beta]1 integrin promote keratinocyte survival; however, the downstream signaling pathways for laminin-5/[alpha]3[beta]1 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 [alpha]3 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 [alpha]3[beta]1 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 [alpha]3[beta]1 integrin and FAK/PI3K/Akt signaling pathways, thereby resulting in cell survival and anti-apoptosis. [PUBLICATION ABSTRACT]