Current Topics in Medicinal Chemistry - Volume 3, Issue 7, 2003

The human genome encodes approximately 100 phosphatases that belong to the protein tyrosine phosphatase (PTP) superfamily, whose substrates range from proteins to phosphoinositides and mRNAs. The hallmark for this superfamily is the active site sequence C(X)5R, also known as the PTP signature motif. The PTPs are key regulatory components in signal transduction pathways and the importance of PTPs in the Read More

The identification of autophosphorylation of the insulin receptor as a pivotal component in the signal transduction induced by insulin, initiated the hunt to identify the tyrosine phosphatase(s) that were responsible for regulating dephosphorylation, and thus inactivation of the receptor. Compelling evidence for the existence of an insulin receptor specific PTP has come from the remarkable phenotype of the PTP1B deficie Read More

Recent studies have demonstrated that protein tyrosine phosphatase 1B (PTP1B) is involved in the down regulation of insulin signaling. Selective inhibitors of PTP1B hold much promise for the treatment of type 2 diabetes mellitus and obesity. Consequently much effort, by both industry and academia, has been devoted towards the development of PTP1B specific inhibitors. This article gives an overview of reports that have a Read More

CD45 is expressed on all nucleated haematopoietic cells and was originally identified as the first and prototypic transmembrane protein tyrosine phosphatase (PTPase). CD45 has been extensively studied for over two decades as a PTPase that functions in antigen receptor signaling by dephosphorylation of Srckinases. CD45 can operate as a positive as well negative regulator of Src-family kinases. In CD45 mutant cell lin Read More

The protein-tyrosine phosphatase (PTP) CD45 serves both positive and negative signaling elements by dephosphorylating regulatory pTyr residues on Srcfamily protein-tyrosine kinases. Although its physiological participation in immune function makes it an important point of intervention for treatment of a variety of inflammatory and immune disorders, comparatively little has been reported on development of CD45 inhibitor Read More

The leukocyte common antigen-related protein, LAR, is a receptor-like protein tyrosine phosphatase (PTP) which has a wide tissue distribution. Post-translational processing cleaves the proprotein into two non-covalently associated subunits, an extracellular subunit resembling a cell adhesion molecule with three immunoglobulinlike domains and eight fibronectin III-like domains, and a phosphatase subunit containing a short ext Read More

This review discusses progress made over the past 10+ years in elucidating the properties, regulation, and function of protein tyrosine phosphatase alpha (PTPα). It is apparent from studies in knockout mice and diverse cell lines that the major action of PTPα is as a positive regulator of src and src family kinases. PTPα dephosphorylates and activates src. In this manner it affects transformation and tumourigenesis, inhibition of p Read More