title: Insulin receptor kinase phosphorylates protein tyrosine phosphatase containing Src homology 2 regions and modulates its PTPase activity in vitro.
abstract: To clarify the role of protein tyrosine phosphatase (PTPase) containing a pair of Src homology 2 (SH2) regions upon insulin signaling, we studied the interactions between the insulin receptor and SH-PTP2 coupled to glutathione-S-transferase. A full length SH-PTP2 was phosphorylated by insulin receptor kinase and associated with the insulin receptor in vitro. The N-terminal SH2 domain was more phosphorylated than the other SH2 domain of SH-PTP2. However, both SH2 domains of SH-PTP2 were necessary for association with insulin receptors. Phosphorylation of the SH2 domains of SH-PTP2 resulted in decreased PTPase activities toward the phosphorylated insulin receptor. These results indicate that the insulin receptor can negatively regulate SH-PTP2 activity by means of phosphorylating the SH2 domains.
authors.affiliation: Third Department of Medicine, Shiga University of Medical Science, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Maegawa
authors.forename: S
authors.initials: S
authors.lastname: Ugi
authors.forename: M
authors.initials: M
authors.lastname: Adachi
authors.forename: Y
authors.initials: Y
authors.lastname: Hinoda
authors.forename: R
authors.initials: R
authors.lastname: Kikkawa
authors.forename: A
authors.initials: A
authors.lastname: Yachi
authors.forename: Y
authors.initials: Y
authors.lastname: Shigeta
authors.forename: A
authors.initials: A
authors.lastname: Kashiwagi
mesh_terms: D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D016391:Genes, src; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D011993:Recombinant Fusion Proteins; D011972:Receptor, Insulin; D017027:Protein Tyrosine Phosphatases