title: Selective down-regulation of the insulin receptor signal by protein-tyrosine phosphatases alpha and epsilon.
abstract: Binding of insulin to its receptor (IR) causes rapid autophosphorylation with concomitant activation of its tyrosine kinase which transmits the signal by phosphorylating cellular substrates. The IR activity is controlled by protein-tyrosine phosphatases, but those directly involved in regulating the insulin receptor and its signaling pathways have not yet been identified. Using baby hamster kidney cells overexpressing the IR and a novel insulin-based selection principle, we established stable cell lines with functionally coupled expression of the IR and protein-tyrosine phosphatases. The two closely related protein-tyrosine phosphatases alpha and epsilon were identified as negative regulators of IR tyrosine kinase.
authors.affiliation: Department of Molecular Biology, Max-Planck-Institut für Biochemie, Martinsried, Germany.
authors.forename: N P
authors.initials: NP
authors.lastname: Møller
authors.forename: K B
authors.initials: KB
authors.lastname: Møller
authors.forename: R
authors.initials: R
authors.lastname: Lammers
authors.forename: A
authors.initials: A
authors.lastname: Kharitonenkov
authors.forename: E
authors.initials: E
authors.lastname: Hoppe
authors.forename: F C
authors.initials: FC
authors.lastname: Wiberg
authors.forename: I
authors.initials: I
authors.lastname: Sures
authors.forename: A
authors.initials: A
authors.lastname: Ullrich
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism*; D007668:Kidney; D007700:Kinetics; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000378:metabolism*; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D007328:Insulin; D007527:Isoenzymes; D011994:Recombinant Proteins; D011972:Receptor, Insulin; D017027:Protein Tyrosine Phosphatases