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Enterocytic differentiation of the human Caco‐2 cell line correlates with alterations in integrin signaling
Author(s) -
Lévy Peggy,
Robin Hélène,
Kornprobst Michel,
Capeau Jacqueline,
Cherqui Gisèle
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199812)177:4<618::aid-jcp12>3.0.co;2-r
Subject(s) - integrin , focal adhesion , microbiology and biotechnology , ptk2 , biology , signal transduction , fibronectin , cellular differentiation , mapk14 , phosphorylation , extracellular matrix , protein kinase a , cell , map kinase kinase kinase , mitogen activated protein kinase kinase , biochemistry , gene
We previously reported that the enterocytic differentiation of human colonic Caco‐2 cells correlated with down‐regulation of fibronectin (FN) and laminin (LN), two extracellular matrix components interacting with cell surface integrin receptors. We now investigated whether Caco‐2 cell differentiation was associated with alterations in integrin signaling with special interest in the expression and activity of focal adhesion kinase (FAK) and mitogen‐activated protein (MAP) kinase. The differentiation of Caco‐2 cells was associated with: (1) down‐regulation of β1 integrin expression at the mRNA and protein levels; (2) increased FAK expression together with decreased FAK autophosphorylation; (3) decreased FAK's ability to associate with PI3‐kinase and pp60 c‐ src ; and (4) increased MAP kinase expression along with decreased MAP activity. In addition, we show that FAK and MAP kinase belong to distinct integrin signaling pathways and that both pathways remain functional during Caco‐2 cell differentiation since the coating of differentiating cells on FN and LN but not on polylysine increased the tyrosine phosphorylation of FAK and of its endogenous substrate paxillin, and stimulated MAP kinase activity. In conclusion, our results provide evidence that FAK and MAP kinase, two signaling molecules activated independently by β1 integrins in Caco‐2 cells, undergo alterations of both expression and activity during the enterocytic differentiation of this cell line. J Cell Physiol 177:618–627, 1998. © 1998 Wiley‐Liss, Inc.