title: Comparative study of three protein-tyrosine phosphatases. Chicken protein-tyrosine phosphatase lambda dephosphorylates c-Src tyrosine 527.
abstract: To examine the substrate preference of protein tyrosine phosphatases (PTPs), we compared the activity of three transmembrane PTPs on dephosphorylation and regulation of c-Src and v-Src: chicken PTP lambda (ChPTP lambda), chicken PTP alpha (ChPTP alpha), and human leukocyte common antigen-related molecule (HLAR). In vitro, all three PTPs dephosphorylated v-Src, but only ChPTP lambda dephosphorylated c-Src. Their activities were also compared in Cos cells coexpressing Src and the phosphatase domains of three PTPs. These domains were fused with peptides for myristylation, so they associated with the cellular membrane. When c-Src was coexpressed with myrPTP lambda, its kinase activity was elevated 3-4-folds. This activation was less obvious when c-Src was coexpressed with myrPTP alpha or myrLAR. Analysis by cyanogen bromide cleavage showed that ChPTP lambda and myrPTP lambda dephosphorylated Tyr-527 of c-Src. Our data demonstrated the different activities of three PTPs on phosphoproteins, suggesting that Src Tyr-527 may require more specific PTP(s) than Src Tyr-416 for dephosphorylation in vivo.
authors.affiliation: Laboratory of Molecular Oncology, Rockefeller University, New York, New York 10021.
authors.forename: K S
authors.initials: KS
authors.lastname: Fang
authors.forename: H
authors.initials: H
authors.lastname: Sabe
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Hanafusa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011956:Receptors, Cell Surface; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D011956:Receptors, Cell Surface; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src); C516841:PTPRA protein, human; D017027:Protein Tyrosine Phosphatases; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4