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	Differentiation state-selective roles of p38 isoforms in human intestinal epithelial cell anoikis
	Vachon, P. H. ; Harnois, C. ; Grenier, A. ; Dufour, G. ; Bouchard, V. ; Han, J. H. ; Landry, J. ; Beaulieu, J. F. ; Vezina, A. ; Dydensborg, A. B. ; Gauthier, R. ; Cote, A. ; Drolet, J. F. ; Lareau, F. ; Han JH(韩家淮)
	2002
关键词	ACTIVATED PROTEIN-KINASE FOCAL ADHESION KINASE SIGNAL-TRANSDUCTION PATHWAYS BCL-X-L DOWN-REGULATION MAP KINASE APOPTOSIS EXPRESSION SURVIVAL INTEGRINS
英文摘要	Background & Aims: Little is known of the signaling events implicated in the induction of human enterocytic anoikis. In the present study, we analyzed the role of the stress-activated protein kinase p38 in this process. Methods: Anoikis was induced in undifferentiated and differentiated enterocytes by inhibition of focal adhesion kinase (Fak; pharmacologic inhibition or overexpression of a dominant negative form) or beta1 integrins (antibody blocking), or by maintaining cells in suspension. Expression/activation parameters of p38 (isoforms alpha, beta, gamma, delta) and of the Fak/phosphatidylinositol-3-kinase (PI3-K)/Akt anoikis-suppressing pathways were analyzed. Kinase activities of p38 isoforms also were blocked by pharmacologic inhibitors or by overexpression of dominant-negative forms. Results: (1) p38 activation is sustained transiently after induction of anoikis in both undifferentiated and differentiated enterocytes; (2) such sustenance of p38 activation is associated with a down-regulation of the Fak/PI3-K/Akt pathway; (3) distinct profiles of p38 isoform expression are exhibited by undifferentiated (alpha, beta, gamma) and differentiated (alpha, gamma, delta) enterocytes; (4) none of the 4 known p38 isoforms was found to promote cell survival in either differentiation state; and (5) only p38beta and p38delta are required specifically for anoikis in undifferentiated and differentiated cells, respectively. Conclusions: Distinct p38 isoforms play a major role in the induction of enterocytic anoikis and the regulation of such selective p38 isoform-mediated anoikis is linked with the state of cell differentiation. These data provide novel insights into the synchronized regulation of cell survival/death required in the epithelial renewal process along the human intestinal crypt-villus axis.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/65775]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Vachon, P. H.,Harnois, C.,Grenier, A.,et al. Differentiation state-selective roles of p38 isoforms in human intestinal epithelial cell anoikis[J],2002.
APA	Vachon, P. H..,Harnois, C..,Grenier, A..,Dufour, G..,Bouchard, V..,...&韩家淮.(2002).Differentiation state-selective roles of p38 isoforms in human intestinal epithelial cell anoikis..
MLA	Vachon, P. H.,et al."Differentiation state-selective roles of p38 isoforms in human intestinal epithelial cell anoikis".(2002).

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