title: Mutant forms of the protein tyrosine phosphatase alpha show differential activities towards intracellular substrates.
abstract: BHK cells overexpressing five million IR (BHK-IR) respond to insulin with reduced growth and detachment from the dish surface. We have recently identified protein tyrosine phosphatase (PTP) alpha as a negative regulator of the insulin receptor (IR) tyrosine kinase that is able to rescue BHK-IR cells from the insulin effect. In this report we describe the effect of several point mutations in PTP alpha on the phosphatase activity and regulation of insulin signaling in BHK-IR cells. Analysis of total cellular phosphotyrosine protein revealed several molecules that were dephosphorylated when PTP alpha or a phosphatase active mutant was overexpressed. By contrast, some proteins were tyrosine phosphorylated as strong or to an even higher extent as in the parental line when PTP alpha Y798F was present. We conclude that mutation of the carboxyterminal tyrosine in PTP alpha uncovers a dual function of this phosphatase in BHK cells: reduction of the IR signal and activation of an endogenous kinase.
authors.affiliation: Max-Planck-Institut für Biochemie, Martinsried, Munich, Germany. rrlammer@med.uni-tuebingen.de
authors.forename: R
authors.initials: R
authors.lastname: Lammers
authors.forename: N P
authors.initials: NP
authors.lastname: Møller
authors.forename: A
authors.initials: A
authors.lastname: Ullrich
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D007328:Insulin / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology; D010766:Phosphorylation; D017354:Point Mutation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism
chemical_list: D007328:Insulin; D011994:Recombinant Proteins; D014443:Tyrosine; D011972:Receptor, Insulin; D017027:Protein Tyrosine Phosphatases