title: Specific inhibition of insulin receptor dephosphorylation by a synthetic dodecapeptide containing sulfotyrosyl residues as phosphotyrosyl mimetic.
abstract: We have synthesized a tris-sulfotyrosyl dodecapeptide (3S-peptide-I) that corresponds to the major autophosphorylation domain within the insulin receptor beta-subunit and showed that it potently inhibited insulin receptor dephosphorylation by protein tyrosine phosphatases (PTPases) in vitro. 3S-peptide-I also inhibited tyrosine dephosphorylation of a synthetic peptide by the recombinant PTPase PTP-1B, indicating that 3S-peptide-I interacts directly with PTPase, causing its inactivation. The peptide had no effect on the activity of serine/threonine phosphatases, PP-1 and PP-2A, or alkaline phosphatase. Furthermore, we found that the introduction of a N-stearyl derivative of 3S-peptide-I in CHO/HIRc cells caused a significant increase in insulin-stimulated phosphorylation of the insulin receptor. In contrast, ligand-stimulated phosphorylation of epidermal growth factor (EGF) receptor in CHO cells overexpressing EGF receptors was not affected by the presence of N-stearyl-3S-peptide-I. These data suggest that by inhibiting dephosphorylation of the insulin receptor in intact cells, 3S-peptide-I may specifically enhance insulin signalling.
authors.affiliation: Diabetes Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Hemantak@vax.grc.nia.nih.gov
authors.forename: H K
authors.initials: HK
authors.lastname: Kole
authors.forename: A S
authors.initials: AS
authors.lastname: Liotta
authors.forename: M J
authors.initials: MJ
authors.lastname: Garant
authors.forename: S
authors.initials: S
authors.lastname: Kole
authors.forename: M
authors.initials: M
authors.lastname: Bernier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011972:Receptor, Insulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D011994:Recombinant Proteins; D066246:ErbB Receptors; D011972:Receptor, Insulin; D017027:Protein Tyrosine Phosphatases