Differences in phosphatase modulation of alpha 4 beta 1 and alpha 5 beta 1integrin-mediated adhesion and migration of B16F1 cells

It is well established that a biphasic relationship exists between the adhe sive strength of beta 1 integrins and their ability to mediate cell movemen t. Thus, cell movement increases progressively with adhesive strength, but beyond a certain point of optimal interaction, cell movement is reduced wit h further increases in adhesive function. The interplay between the various kinase and phosphatase activities provides the balance in beta 1 integrin- mediated cell adhesion and migration. In the present study, the significanc e of protein tyrosine phosphatases (PTP) and ser/thr protein phosphatases ( PP) in alpha 4 beta 1 and alpha 5 beta 1 integrin-mediated mouse melanoma B 16F1 cell anchorage and migration on fibronectin was characterized using ph osphatase inhibitors. At low fibronectin concentration, alpha 5 beta 1 func tioned as the predominant receptor for cell movement; a role for alpha 4 be ta 1 in B16F1 cell migration increased progressively with fibronectin conce ntration. Treatment of B16F1 cells with PTP inhibitors, sodium orthovanadat e (Na3VO4) and phenylarsine oxide (PAO), or PP-1/2A inhibitor, okadaic acid (OA), abolished cell movement. Inhibition of cell movement by PAO and OA w as associated by a reduction in the adhesive strength of alpha 4 beta 1 and alpha 5 beta 1. In contrast, treatment of B16F1 cells with Na3VO4 resulted in selective stimulation of the adhesive function of alpha 5 beta 1, but n ot alpha 4 beta 1. Therefore, our results demonstrate that (i) both PTP and PP-1/2A have roles in cell movement, (ii) modulation of cell movement by P TP and PP-1/2A may involve either a stimulation or reduction of beta 1 inte grin adhesive strength, and (iii) distinct phosphatase-mediated signaling p athways for differential regulation of the various beta 1 integrins exist.