Protein Tyrosine Phosphatases: Critical Regulators of Signaling in Cancer

Abstract

The protein tyrosine phosphatases (PTPs) are now recognized as critical regulators of signal transduction under normal and pathophysiological conditions. These enzymes belong to a family of cysteine‐dependent phosphatases, which are characterized by a conserved ‘C[X]5R’ motif and hydrolyze phosphoester bonds in proteins and non‐protein substrates. Overall, the objective of the lab is to examine PTP regulation and function in cell and animal models, and to define the role of PTPs in critical tyrosine phosphorylation‐dependent signaling events in human disease. Currently, there are four broad areas of research in the lab covering (i) functional analysis of members of the PTP family, (ii) redox regulation of PTP function, (iii) development of novel approaches to therapeutic intervention in PTP function, and (iv) characterization of a knockout mouse model to define the function of JSP1, a member of the PTP family that is a novel regulator of MAP kinase signaling. I will discuss how these studies are leading to identification of novel therapeutic targets from among the PTP family. There is a perception in industry that the members of the PTP family are “undruggable”; however, I will illustrate how a detailed understanding of the structure and function of PTPs has suggested new approaches to the development of small molecule drug candidates that target these enzymes.