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α 5 β 1 integrin stimulates Bcl‐2 expression and cell survival through Akt, focal adhesion kinase, and Ca 2+ /calmodulin‐dependent protein kinase IV
Author(s) -
Lee ByungHeon,
Ruoslahti Erkki
Publication year - 2005
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20488
Subject(s) - protein kinase b , focal adhesion , microbiology and biotechnology , pi3k/akt/mtor pathway , integrin , camk , biology , signal transduction , kinase , creb , protein kinase a , chemistry , cancer research , transcription factor , receptor , biochemistry , gene , autophosphorylation
CHO cells expressing α 5 β 1 integrin are more resistant to apoptosis and express more Bcl‐2 than the same cells engineered to express α v β 1 or cytoplasmically truncated α 5 Δcβ 1 integrin as their main fibronectin receptor. The Bcl‐2 up‐regulation by α 5 β 1 is mediated, at least in part, by the focal adhesion kinase (FAK) and phosphatidylinositol‐3 kinase (PI3K)/Akt pathways. Here, we show that integrin‐mediated activation of Ca 2+ /calmodulin‐dependent protein kinase (CaMK) IV, and the NF‐κB and CREB transcription factors also enhance the integrin‐dependent regulation of Bcl‐2 expression in the α 5 β 1 cells. A forkhead transcription factor, which is inactivated by Akt, blocked Bcl‐2 expression. The FAK pathway was found to be defective in both the α v β 1 and α 5 Δcβ 1 cells. These cell lines differed from one another in two Bcl‐2‐regulating pathways: adhesion through α v β 1 failed to activate Akt, allowing forkhead to suppress Bcl‐2 transcription, whereas α 5 Δcβ 1 did not activate NF‐κB and CREB, presumably because CaMK IV was not activated. Our results indicate that three pathways, the FAK, PI3K/Akt, and CaMK IV mediate the survival‐supporting activity of α 5 β 1 integrin. © 2005 Wiley‐Liss, Inc.