Protein tyrosine phosphatases: their role in insulin action and potential as drug targets
- 23 February 1999
- journal article
- Published by Informa Healthcare in Expert Opinion on Investigational Drugs
- Vol. 8 (2) , 139-160
- https://doi.org/10.1517/13543784.8.2.139
Abstract
Protein tyrosine phosphatases (PTPases) are the enzymes responsible for the selective dephosphorylation of tyrosine residues. PTPases function to regulate a wide array of biological responses mediated by growth factors and other stimuli by balancing the cellular level of phosphotyrosine in concert with their counterparts, protein tyrosine kinases. The important roles which PTPases play in regulating intracellular signalling and, ultimately, biological function along with the recent availability of information regarding their structural features has highlighted them as potential targets for pharmacological modulation. This is demonstrated by the increased level of activity directed towards the identification of novel small-molecule PTPase inhibitors. The rationale and potential utility of this drug discovery approach is discussed here, with particular emphasis on its application for the treatment of insulin resistance and Type 2 diabetes.Keywords
This publication has 97 references indexed in Scilit:
- Protein-Tyrosine Phosphatases: Biological Function, Structural Characteristics, and Mechanism of CatalysisCritical Reviews in Biochemistry and Molecular Biology, 1998
- The Protein Tyrosine Phosphatase LAR Has a Major Impact on Insulin Receptor DephosphorylationBiochemical and Biophysical Research Communications, 1997
- Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non—insulin-dependent diabetes mellitusMetabolism, 1996
- The Transmembrane Protein-tyrosine Phosphatase LAR Modulates Signaling by Multiple Receptor Tyrosine KinasesJournal of Biological Chemistry, 1996
- Why Is Phosphonodifluoromethyl Phenylalanine a More Potent Inhibitory Moiety Than Phosphonomethyl Phenylalanine Toward Protein-Tyrosine PhosphatasesBiochemical and Biophysical Research Communications, 1995
- Modulation of insulin action by vanadate: evidence of a role for phosphotyrosine phosphatase activity to alter cellular signalingMolecular and Cellular Biochemistry, 1995
- Insulin-like actions of vanadate are mediated in an insulin-receptor-independent manner via non-receptor protein tyrosine kinases and protein phosphotyrosine phosphatasesMolecular and Cellular Biochemistry, 1995
- Potent Inhibition of Insulin Receptor Dephosphorylation by a Hexamer Peptide Containing the Phosphotyrosyl Mimetic F2PmpBiochemical and Biophysical Research Communications, 1994
- Identification of Protein-Tyrosine Phosphatases Prevalent in Adipocytes by Molecular CloningBiochemical and Biophysical Research Communications, 1994
- Dephosphorylation of the hepatic insulin receptor: Absence of intrinsic phosphatase activity in purified receptorsBiochemical and Biophysical Research Communications, 1983