Protein tyrosine phosphatase alpha (PTP alpha): A src family kinase activator and mediator of multiple biological effects

This review discusses progress made over the past 10+ years in elucidating the properties, regulation, and function of protein tyrosine phosphatase alpha (PTPalpha). It is apparent from studies in knockout mice and diverse cell lines that the major action of PTPalpha is as a positive regulator of src and src family kinases. PTPalpha dephosphorylates and activates src. In this manner it affects transformation and tumourigenesis, inhibition of proliferation and cell cycle arrest, mitotic activation of src, integrin signaling, neuronal differentiation and outgrowth, and ion channel activity. PTPalpha may well modulate additional processes, including insulin signaling, and have other targets besides src family kinases. As an important modulator of several specific cell signaling pathways, PTPa has promise as a target for drug discovery. Continued research on the physiological and pathological activities of PTPa is necessary to define the therapeutic potential of PTPalpha-directed pharmacologicals.