The 64-kDa Protein that Associates with the Platelet-Derived Growth Factor Receptor β Subunit via Tyr-1009 is the SH2-Containing Phosphotyrosine Phosphatase Syp

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 15; pp. 6939 - 6943
• Main Authors: Kazlauskas, Andrius, Feng, Gen-Sheng, Pawson, Tony, Valius, Mindaugas
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.08.1993; National Acad Sciences
• Subjects: Antiserum; Binding sites; Biological and medical sciences; Cell receptors; Cell structures and functions; Fundamental and applied biological sciences. Psychology; Gels; Growth factor receptors; Hep G2 cells; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Humans; In Vitro Techniques; Intracellular Signaling Peptides and Proteins; Macromolecular Substances; Medical research; Molecular and cellular biology; Peptide Mapping; Phosphatases; Phosphorylation; Phosphotyrosine; Protein Binding; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases - metabolism; Proteins; Receptors; Receptors, Platelet-Derived Growth Factor - metabolism; Tumor Cells, Cultured; Tyrosine - analogs & derivatives; Tyrosine - metabolism; Human; Phosphorylation; Hepatocyte; Enzyme; Beta-Peptide chain; Molecular association; Binding site; Platelet derived growth factor; Protein-tyrosine-phosphatase; Biological receptor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.15.6939

Ligand-stimulated autophosphorylation of the platelet-derived growth factor receptor (PDGFR) β subunit creates a number of binding sites for SH2-containing proteins. One of the PDGFR-associated proteins is a 64-kDa protein of unknown identity and function. We present data indicating that the 64-kDa protein that associates with the activated PDGFR is Syp (also called SH-PTP2, PTP-1D, or SH-PTP3), the ubiquitously expressed 64-kDa SH2-containing proteintyrosine phosphatase. Phosphorylation of Tyr-1009 in the C terminus of the PDGFR is required for the stable association of Syp, suggesting that phosphorylation of this residue creates a binding site for the Syp SH2 domains. Although Syp stably associates with the PDGFR, this event is not required for PDGF-stimulated tyrosine phosphorylation of Syp. These data raise the interesting possibility that protein-tyrosine phosphatases contribute to the intracellular relay of biological signals originating from receptor tyrosine kinases such as the PDGFR.