PROTEIN-TYROSINE-PHOSPHATASE 1B INTERACTS WITH AND IS TYROSINE-PHOSPHORYLATED BY THE EPIDERMAL GROWTH-FACTOR RECEPTOR

We used a substrate-trapping technique to search for substrates of pro tein tyrosine phosphatase (PTP) 1B. A catalytically inactive form of t his enzyme forms a stable, phosphotyrosine-dependent complex with epid ermal growth factor receptor (EGFR) both in vitro and in cells. PTP1B also interacts with activated platelet-derived growth factor receptor (PDGFR) but not with colony-stimulating factor 1 receptor (CSF-IR). Af ter binding to EGFR, PTP1B becomes tyrosine-phosphorylated at Tyr-66, a site that conforms to the consensus binding sequence for the Src hom ology 2 (SH2) domains of the adapter protein Grb2. This tyrosine phosp horylation is correlated with a 3-fold increase in PTP catalytic activ ity. These findings suggest that PTP1B selectively regulates specific activated receptor protein tyrosine kinases (RPTKs) in vivo and might itself be regulated by such receptors.