Enterocytic differentiation of the human Caco-2 cell line correlates with alterations in integrin signaling

We previously reported that the enterocytic differentiation of human coloni c Caco-2 cells correlated with down-regulation of fibronectin (FN) and lami nin (LN), two extracellular matrix components interacting with cell surface integrin receptors. We now investigated whether Caco-2 cell differentiatio n was associated with alterations in integrin signaling with special intere st in the expression and activity of focal adhesion kinase (FAK) and mitoge n-activated protein (MAP) kinase. The differentiation of Caco-2 cells was a ssociated with: 1) down-regulation of beta 1 integrin expression at the mRN A and protein levels, 2) increased FAK expression together with decreased F AK autophosphorylation; 3) decreased FAK's ability to associate with PI3-ki nase and pp60(c-src); and 4) increased MAP kinase expression along with dec reased MAP activity. In addition, we show that FAK and MAP kinase belong to distinct integrin signaling pathways and that both pathways remain functio nal during Caco-2 cell differentiation since the coating of differentiating cells on FN and LN but not on polylysine increased the tyrosine phosphoryl ation of FAK and of its endogenous substrate paxillin, and stimulated MAP k inase activity. In conclusion, our results provide evidence that FAK and MA P kinase, two signaling molecules activated independently by beta 1 integri ns in Caco-2 cells, undergo alterations of both expression and activity dur ing the enterocytic differentiation of this cell line. J Cell Physiol 177:6 18-627, 1998. (C) 1998 Wiley-Liss, Inc.