Receptor Protein-tyrosine Phosphatase α Regulates Focal Adhesion Kinase Phosphorylation and ErbB2 Oncoprotein-mediated Mammary Epithelial Cell Motility

We investigated the role of protein-tyrosine phosphatase (PTP) in regulating signaling by the ErbB2 oncoprotein in mammary epithelial cells. Using this model, we demonstrated that activation of ErbB2 led to the transient inactivation of PTP, suggesting that attenuation of PTP activity may contribute to enhanced ErbB2 signaling. Furthermore, RNAi-induced suppression of PTP led to increased cell migration in an ErbB2-dependent manner. The ability of ErbB2 to increase cell motility in the absence of PTP was characterized by prolonged interaction of GRB7 with ErbB2 and increased association of ErbB2 with a 1-integrin-rich complex, which depended on GRB7-SH2 domain interactions. Finally, suppression of PTP resulted in increased phosphorylation of focal adhesion kinase on Tyr-407, which induced the recruitment of vinculin and the formation of a novel focal adhesion kinase complex in response to ErbB2 activation in mammary epithelial cells. Collectively, these results reveal a new role for PTP in the regulation of motility of mammary epithelial cells in response to ErbB2 activation.