The 64-kDa protein that associates with the platelet-derived growth factor receptor beta subunit via Tyr-1009 is the SH2-containing phosphotyrosine phosphatase Syp.
Ligand-stimulated autophosphorylation of the platelet-derived growth factor receptor (PDGFR) beta 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 protein-tyrosine 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.
Kazlauskas
A
A
National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Feng
G S
GS
Pawson
T
T
Valius
M
M
D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D010449:Peptide Mapping; D010766:Phosphorylation; D019000:Phosphotyrosine; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D019000:Phosphotyrosine; D014443:Tyrosine; D017479:Receptors, Platelet-Derived Growth Factor; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases