Protein Tyrosine Phosphatases in Metabolism: A New Frontier for Therapeutics

Abstract

The increased prevalence of chronic metabolic disorders, including obesity and type 2 diabetes and their associated comorbidities, are among the world's greatest health and economic challenges. Metabolic homeostasis involves a complex interplay between hormones that act on different tissues to elicit changes in the storage and utilization of energy. Such processes are mediated by tyrosine phosphorylation-dependent signaling, which is coordinated by the opposing actions of protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Perturbations in the functions of PTPs can be instrumental in the pathophysiology of metabolic diseases. The goal of this review is to highlight key advances in our understanding of how PTPs control body weight and glucose metabolism, as well as their contributions to obesity and type 2 diabetes. The emerging appreciation of the integrated functions of PTPs in metabolism, coupled with significant advances in pharmaceutical strategies aimed at targeting this class of enzymes, marks the advent of a new frontier in combating metabolic disorders.