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 protein tyrosine phosphatase (PTP) 1B. A catalytically inactive form of this enzyme forms a stable, phosphotyrosine-dependent complex with epidermal 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-1R). After binding to EGFR, PTP1B becomes tyrosine-phosphorylated at Tyr-66, a site that conforms to the consensus binding sequence for the Src homology 2 (SH2) domains of the adapter protein Grb2. This tyrosine phosphorylation is correlated with a 3-fold increase in PTP catalytic activity. These findings suggest that PTP1B selectively regulates specific activated receptor protein tyrosine kinases (RPTKs) in vivo and might itself be regulated by such receptors.
Liu
F
F
Chemistry Department, Temple University, Philadelphia, PA 19122, USA.
Chernoff
J
J
D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D016184:Receptors, Colony-Stimulating Factor / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured
D016184:Receptors, Colony-Stimulating Factor; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; D005982:Glutathione Transferase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D017027:Protein Tyrosine Phosphatases