Site-Selective Regulation of Platelet-Derived Growth Factor Receptor Tyrosine Phosphorylation by T-Cell Protein

The platelet-derived growth factor (PDGF) receptor mediates mitogenic and chemotactic signals. Like other tyrosine kinase receptors, the PDGF receptor is negatively regulated by protein tyrosine phosphatases (PTPs). To explore whether T-cell PTP (TC-PTP) negatively regulates the PDGF receptor, we compared PDGF receptor tyrosine phosphorylation in wild-type and TC-PTP knockout (ko) mouse embryos. PDGF receptors were hyperphosphorylated in TC-PTP ko embryos. Fivefold-higher ligand-induced receptor phos-phorylation was observed in TC-PTP ko mouse embryo fibroblasts (MEFs) as well. Reexpression of TC-PTP partly abolished this difference. As determined with site-specific phosphotyrosine antibodies, the extent of hyperphosphorylation varied among different autophosphorylation sites. The phospholipase C1 binding site Y1021, previously implicated in chemotaxis, displayed the largest increase in phosphorylation. The increase in Y1021 phosphorylation was accompanied by increased phospholipase C1 activity and migratory hyperre-sponsiveness to PDGF. PDGF receptor tyrosine phosphorylation in PTP-1B ko MEFs but not in PTP ko MEFs was also higher than that in control cells. This increase occurred with a site distribution different fro