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Expert Opin Investig Drugs. 1999 Feb;8(2):139-60.

Protein tyrosine phosphatases: their role in insulin action and potential as drug targets.

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Diabetes Program, SUGEN, Inc., 230 East Grand Avenue, San Francisco, CA 94080, USA.


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.


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