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dc.contributor.authorVachon, P. H.zh_CN
dc.contributor.authorHarnois, C.zh_CN
dc.contributor.authorGrenier, A.zh_CN
dc.contributor.authorDufour, G.zh_CN
dc.contributor.authorBouchard, V.zh_CN
dc.contributor.authorHan, J. H.zh_CN
dc.contributor.authorLandry, J.zh_CN
dc.contributor.authorBeaulieu, J. F.zh_CN
dc.contributor.authorVezina, A.zh_CN
dc.contributor.authorDydensborg, A. B.zh_CN
dc.contributor.authorGauthier, R.zh_CN
dc.contributor.authorCote, A.zh_CN
dc.contributor.authorDrolet, J. F.zh_CN
dc.contributor.authorLareau, F.zh_CN
dc.contributor.author韩家淮zh_CN
dc.date.accessioned2013-12-12T02:24:41Z
dc.date.available2013-12-12T02:24:41Z
dc.date.issued2002zh_CN
dc.identifier.citationGastroenterology,123(6):1980-1991zh_CN
dc.identifier.issn0016-5085zh_CN
dc.identifier.otherISI:000179545300029zh_CN
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/65775
dc.description.abstractBackground & 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.zh_CN
dc.language.isoen_USzh_CN
dc.subjectACTIVATED PROTEIN-KINASEzh_CN
dc.subjectFOCAL ADHESION KINASEzh_CN
dc.subjectSIGNAL-TRANSDUCTION PATHWAYSzh_CN
dc.subjectBCL-X-Lzh_CN
dc.subjectDOWN-REGULATIONzh_CN
dc.subjectMAP KINASEzh_CN
dc.subjectAPOPTOSISzh_CN
dc.subjectEXPRESSIONzh_CN
dc.subjectSURVIVALzh_CN
dc.subjectINTEGRINSzh_CN
dc.titleDifferentiation state-selective roles of p38 isoforms in human intestinal epithelial cell anoikiszh_CN
dc.typeArticlezh_CN


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