MAPK-specific tyrosine phosphatases: new targets for drug discovery?

Barr, Alastair J. and Knapp, Stefan (2006) MAPK-specific tyrosine phosphatases: new targets for drug discovery? Trends in Pharmacological Sciences, 27 (10). pp. 525-530. ISSN 0165-6147

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Protein tyrosine phosphatases (PTPs) have key roles in a diverse range of cellular processes, and their dysregulation is associated with several human diseases. Many PTPs are recognized as potential drug targets; however, inhibitor development has focused only on a small number of enzymes, most notably PTP1B for type II diabetes and obesity, and MKP1 and CDC25 for cancer. The future challenge of selective-inhibitor development for PTPs will be significantly facilitated by the recent rapid progress in the structural biology of the ‘PTPome’. In this article, we focus on the family of mitogen-activated protein kinase (MAPK)-specific tyrosine phosphatases – PTPN5 [also called striatal-enriched phosphatase (STEP)], PTPN7 (also called hematopoietic PTP) and PTPRR (also called PC12 PTP or STEP-like PTP) – and discuss approaches for achieving selectivity for the MAPK-PTPs at the molecular level using recently determined high-resolution X-ray crystal structures. We believe that the development of specific inhibitors would provide a valuable set of experimental pharmacological tools for investigating the physiological role of these phosphatases and exploring their emerging role in human disease.

Item Type: Article
Subjects: University of Westminster > Science and Technology > Life Sciences, School of (No longer in use)
Depositing User: Rachel Wheelhouse
Date Deposited: 20 Jul 2012 14:08
Last Modified: 20 Jul 2012 14:08

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