FOCAL ADHESION KINASE PP125(FAK) AND THE BETA-1 INTEGRIN SUBUNIT ARE CONSTITUTIVELY COMPLEXED IN HACAT CELLS

Binding of integrins to the extracellular matrix (ECM) activates vario us signal transduction pathways and regulates gene expression in many cell types. Integrin-dependent cytoplasmic protein/protein interaction s are necessary for activation of those signal transduction cascades. In our studies we investigated a possible association of pp125(FAK), a n adhesion involved tyrosine kinase, with the integrin beta 1 subunit. Further we wanted to know to which extent protein tyrosine phosphoryl ation affects cell adhesion to the ECM and the possible beta 1 integri n/pp125(FAK) complex. We were able to show that in HaCaT cells (a huma n keratinocyte derived cell line) the integrin beta subunit is associa ted with tyrosine kinase pp125(FAK). This association was observed in ECM-adherent cells and nonadherent cells and is independent of tyrosin e phosphorylation. However, cell adhesion of HaCaT cells to specific s ubstrates requires tyrosine phosphorylation since genistein treatment that blocks phosphorylation of many cellular proteins as pp125(FAK) le d to a reduced substrate adhesion. (C) 1998 Academic Press.