NERVE GROWTH-FACTOR STIMULATES TYROSINE PHOSPHORYLATION AND ACTIVATION OF SRC HOMOLOGY-CONTAINING PROTEIN-TYROSINE-PHOSPHATASE-1 IN PC12 CELLS

Rat PC12 cells respond to extracellular peptide growth factors in at l east two distinct ways, When treated with nerve growth factor (NGF) PC 12 cells exit the cell cycle and differentiate to a neuronal phenotype , whereas when treated with epidermal growth factor, they proliferate, We examined the potential role of Src homology 2 (SH2)-containing pro tein tyrosine phosphatases (PTPs) in the differentiation process, PC12 cells express substantial amounts of both SH-PTP1 and 2. SH-PTP1, but not SH-PTP2, becomes tyrosine phosphorylated following NGF, but not e pidermal growth factor treatment, The enzymatic activity of SH-PTP1 to ward an exogenous substrate following NGF treatment is increased 2-fol d. We found that SH-PTP1 binds to the NGF receptor TrkA in vitro and t hat anti-TrkA immunoprecipitates have PTP activity. These results show that SH-PTP1 is differentially phosphorylated and activated by NGF in PC12 cells and suggest that this activation may play a role in NGF-in duced differentiation.