['Structural requirements for the beta1 integrin functions in cell adhesion, spreading and signaling have been well documented mainly for fibroblasts. In this study, we examined the reason for the reduced surface expression of beta1 integrin in human breast cancer MCF-7 cells compared to normal human breast epithelial (HBE) cells, both of which adhered to collagen type IV.', 'The beta1 integrin immunoprecipitates from either HBE or MCF-7 cells involved alpha-actinin while actin coprecipitated with beta1 integrin from HBE cells but not from MCF-7 cells. Immunoblotting using the anti-phosphotyrosine (PY) antibody indicated the phosphorylation of beta1 integrin at least at tyrosine in both cells. Dephosphorylation of beta1 integrin from HBE cells by protein tyrosine phosphatase (PTP), but not by protein serine/threonine phosphatase (PP), caused dissociation of actin from beta1 integrin, although dephosphorylation of it from MCF-7 cells by either PTP or PP caused association of the two proteins. In MCF-7 cells beta1 integrin coprecipitated doublet of proteins having the Ca2+/calmodulin-dependent protein kinase (CaMK) II activity that was susceptible to KN-62, a specific inhibitor of CaMKII.'] Is the linkage between beta1 integrin and the actin cytoskeleton differentially regulated by tyrosine and serine/threonine phosphorylation of beta1 integrin in normal and cancerous human breast cells?