It is well established that a biphasic relationship exists between the adhesive strength of beta1
integrins and their ability to mediate cell movement. Thus, cell movement increases progressively with adhesive strength, but beyond a certain point of optimal interaction, cell movement is reduced with further increases in adhesive function. The interplay between the various
kinase and
phosphatase activities provides the balance in
beta1 integrin-mediated cell adhesion and migration. In the present study, the significance of
protein tyrosine phosphatases (PTP) and ser/thr
protein phosphatases (PP) in alpha4beta1 and
alpha5beta1 integrin-mediated mouse
melanoma B16F1 cell anchorage and migration on
fibronectin was characterized using
phosphatase inhibitors. At low
fibronectin concentration, alpha5beta1 functioned as the predominant receptor for cell movement; a role for alpha4beta1 in B16F1 cell migration increased progressively with
fibronectin concentration. Treatment of B16F1 cells with PTP inhibitors,
sodium orthovanadate (Na3VO4) and
phenylarsine oxide (PAO), or PP-1/2A inhibitor,
okadaic acid (OA), abolished cell movement. Inhibition of cell movement by PAO and OA was associated by a reduction in the adhesive strength of alpha4beta1 and alpha5beta1. In contrast, treatment of B16F1 cells with Na3VO4 resulted in selective stimulation of the adhesive function of alpha5beta1, but not alpha4beta1. Therefore, our results demonstrate that (i) both PTP and PP-1/2A have roles in cell movement, (ii) modulation of cell movement by PTP and PP-1/2A may involve either a stimulation or reduction of
beta1 integrin adhesive strength, and (iii) distinct
phosphatase-mediated signaling pathways for differential regulation of the various beta1
integrins exist.