Protein tyrosine phosphatases: from genes, to function, to disease

Abstract

The protein tyrosine phosphatase (PTP) superfamily of enzymes functions in a coordinated manner with the protein tyrosine kinases to control signalling pathways that underlie a number of fundamental physiological processes. In this review, I describe recent breakthroughs in our understanding of the role of the PTPs in the regulation of signal transduction and the aetiology of human disease. The topics covered include: An overview of the composition of the PTP superfamily. The nature and function of pseudophosphatase PTPs, which maintain the PTP fold but lack crucial features that are required for enzymatic activity. The regulation and function of receptor PTPs. This includes discussion of the role of ligand binding and receptor-type (RPTP) dimerization in control of activity, as well as the identity of such ligands and some of the signalling events they regulate. Regulation of PTP function by reversible oxidation and its potential to represent a new tier of control of tyrosine-phosphorylation-dependent signal transduction. Links between aberrant PTP function and human disease, including discussion of the potential for therapeutic intervention at the level of PTP function.