HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kole, H. K. Articles by Bernier, M. Search for Related Content PubMed PubMed Citation Articles by Kole, H. K. Articles by Bernier, M. Social Bookmarking                      What's this?

Volume 271, Number 24, Issue of June 14, 1996 pp. 14302-14307
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

A Peptide-based Protein-tyrosine Phosphatase Inhibitor Specifically Enhances Insulin Receptor Function in Intact Cells

(Received for publication, September 12, 1995, and in revised form, March 29, 1996)

From the Diabetes Section, Laboratory of Clinical Physiology, NIA, National Institutes of Health, Baltimore, Maryland 21224

3S-peptide-I is a synthetic tris-sulfotyrosyl dodecapeptide corresponding to the major site of insulin receptor autophosphorylation that potently inhibits dephosphorylation of the insulin receptor in a cell-free system and in digitonin-permeabilized Chinese hamster ovary (CHO) cells overexpressing the human insulin receptors (CHO/HIRc cells) (Liotta, A. S., Kole, H. K., Fales, H. M., Roth, J., and Bernier, M. (1994) J. Biol. Chem. 269, 22996-23001). In the present study, we found that 3S-peptide-I was not capable of inhibiting dephosphorylation of the epidermal growth factor (EGF) receptors in digitonin-permeabilized CHO cells that overexpress human EGF receptors (CHO/EGF-R cells). Moreover, the addition of a N-stearyl derivative of 3S-peptide-I to intact CHO/HIRc cells caused a concentration-dependent increase in insulin-stimulated phosphorylation of the insulin receptor, with a maximum effect (~2.7-fold) at 50 µM. In contrast, ligand-stimulated EGF receptor phosphorylation in CHO/EGF-R cells was not affected by the presence of stearyl 3S-peptide-I. Furthermore, treatment of CHO/HIRc cells with this N-stearyl peptide led to a significant enhancement of the insulin-induced association of phosphatidylinositol (PI) 3-kinase activity with insulin receptor substrate 1 and the activation of mitogen-activated protein kinase. However, stearyl 3S-peptide-I had no effect on the EGF-stimulated activation of PI-3-kinase and mitogen-activated protein kinase in CHO/EGF-R cells. These data indicate that this tris-sulfotyrosyl dodecapeptide selectively enhances insulin signal transduction by specifically inhibiting dephosphorylation of the insulin receptor in intact cells.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Walchli, X. Espanel, A. Harrenga, M. Rossi, G. Cesareni, and R. H. van Huijsduijnen Probing Protein-tyrosine Phosphatase Substrate Specificity Using a Phosphotyrosine-containing Phage Library J. Biol. Chem., January 2, 2004; 279(1): 311 - 318. [Abstract] [Full Text] [PDF]

				H. S. Andersen, L. F. Iversen, C. B. Jeppesen, S. Branner, K. Norris, H. B. Rasmussen, K. B. Moller, and N. P. H. Moller 2-(Oxalylamino)-Benzoic Acid Is a General, Competitive Inhibitor of Protein-tyrosine Phosphatases J. Biol. Chem., March 15, 2000; 275(10): 7101 - 7108. [Abstract] [Full Text] [PDF]

				J.-L. Wang, Z.-J. Zhang, S. Choksi, S. Shan, Z. Lu, C. M. Croce, E. S. Alnemri, R. Korngold, and Z. Huang Cell Permeable Bcl-2 Binding Peptides: A Chemical Approach to Apoptosis Induction in Tumor Cells Cancer Res., March 1, 2000; 60(6): 1498 - 1502. [Abstract] [Full Text]

				B. T. Solow, S. Harada, B. J. Goldstein, J. A. Smith, M. F. White, and L. Jarett Differential Modulation of the Tyrosine Phosphorylation State of the Insulin Receptor by IRS (Insulin Receptor Subunit) Proteins Mol. Endocrinol., October 1, 1999; 13(10): 1784 - 1798. [Abstract] [Full Text]

				M. Naramura, H. K. Kole, R.-J. Hu, and H. Gu Altered thymic positive selection and intracellular signals in Cbl-deficient mice PNAS, December 22, 1998; 95(26): 15547 - 15552. [Abstract] [Full Text] [PDF]

				R. Perfetti, W. Lee-Kwon, C. Montrose-Rafizadeh, and M. Bernier Overexpression and Activation of the Insulin Receptor Enhances Expression of ERCC-1 Messenger Ribonucleic Acid in Cultured Cells Endocrinology, May 1, 1997; 138(5): 1829 - 1835. [Abstract] [Full Text] [PDF]

				H. K. Kole, A. S. Liotta, S. Kole, J. Roth, C. Montrose-Rafizadeh, and M. Bernier A Synthetic Peptide Derived from a COOH-terminal Domain of the Insulin Receptor Specifically Enhances Insulin Receptor Signaling J. Biol. Chem., December 6, 1996; 271(49): 31619 - 31626. [Abstract] [Full Text] [PDF]