Protein Tyrosine Phosphatases as Therapeutic Targets

Abstract

The protein tyrosine phosphatases (PTPs) are a family of regulatory enzymes that are critical for a wide variety of cellular functions. During the last decade, the interest and findings on the role of PTPs in signal transduction have increased tremendously. Initially, these enzymes were viewed as negative regulators of signaling cascades triggered by protein tyrosine kinases (PTKs). It is now well established that several members of the PTP family are also positive regulators of several signaling pathways. Compelling evidence from biochemical, cell biology, and gene-targeting studies has implicated PTPs in multiple processes that include metabolism, development, immunity, and cancer. Indeed, mutations in several PTP genes are associated with human disorders. Moreover, many pathological organisms have acquired specific PTPs or target host cell PTPs to increase virulence and promote their own propagation. Taken together, these findings identified specific PTPs as significant targets for the therapeutic intervention in human diseases. For instance, the discovery that PTP1B is a negative regulator of insulin signaling revealed that this molecule is an attractive target for the treatment of insulin-resistant diseased states like type 2 diabetes mellitus and obesity. At the other end of the spectrum, the phosphatases of the CDC25 subfamily, which are key regulators of the cell cycle, are currently targeted for the treatment of cancers. These are just two examples that are discussed in this review. Although, we are still in the infancy in understanding PTP function, several of these enzymes are currently intensely investigated for their potential therapeutic values.