title: Receptor-binding, tyrosine phosphorylation and chromosome localization of the mouse SH2-containing phosphotyrosine phosphatase Syp.
abstract: The murine phosphotyrosine phosphatase, Syp, is a widely-expressed cytoplasmic enzyme that contains two SH2 domains. Syp is physically associated with activated receptors for epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), apparently through its SH2 domains. This phosphatase is rapidly phosphorylated in cells treated with PDGF or EGF, and is constitutively phosphorylated in v-src transformed cells. Here we report that either the N-terminal or C-terminal Syp SH2 domain alone bound to the activated beta PDGF receptor or EGF-receptor in vitro, and that the two SH2 domains linked together exhibited synergistic binding. Substitution of the Tyr1009 autophosphorylation site in the C-terminal tail of activated beta PDGFR with Phe abolished the in vitro binding of either SH2 domain to the activated receptor. A 9 amino acid phosphopeptide corresponding to the Tyr1009 autophosphorylation site of the beta PDGFR inhibited association of the Syp SH2 domains with the receptor. These results indicate that the Syp SH2 domains have an intrinsic specificity for the Tyr1009 autophosphorylation site of the beta PDGFR that dictates binding of the intact Syp phosphatase, and suggest that both SH2 domains have a related binding specificity. Phosphoamino acid analysis of Syp from PDGF-stimulated cells indicated that PDGF primarily induces Syp phosphorylation on tyrosine residues. The mouse Syp gene has been mapped to chromosome 5F region by the fluorescence in situ hybridization. These findings suggest specific functions for Syp in signal transduction downstream of receptor tyrosine kinases.
authors.affiliation: Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: G S
authors.initials: GS
authors.lastname: Feng
authors.forename: R
authors.initials: R
authors.lastname: Shen
authors.forename: H H
authors.initials: HH
authors.lastname: Heng
authors.forename: L C
authors.initials: LC
authors.lastname: Tsui
authors.forename: A
authors.initials: A
authors.lastname: Kazlauskas
authors.forename: T
authors.initials: T
authors.lastname: Pawson
mesh_terms: D000818:Animals; D001665:Binding Sites; D002874:Chromosome Mapping; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D012680:Sensitivity and Specificity
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D066246:ErbB Receptors; 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; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases