Protein Tyrosine Phosphatases: A new paradigm in an old signaling system?

Protein Tyrosine Phosphatases reverse cellular signals initiated by growth factors receptors and other tyrosine kinases by dephosphorylating phosphotyrosine on target proteins. The activity of these enzymes is crucial for maintaining cell homeostasis, yet these enzymes have been often dismissed as humble house-keeping proteins. Understandably, mutations and changes in expression patterns of Protein Tyrosine Phosphatases are implicated in tumorigenesis and various carcinomas. The conserved nature of their catalytic domains makes drug discovery a challenging pursuit. In this review, we focus on describing the various classes of Protein Tyrosine Phosphatases and their catalytic domains. We also summarize their role in cancer and neurodegenerative diseases using specific members as the model system. Finally, we explain the dichotomy in the biological role of catalytically active vs the pseudoenzyme forms of Protein Tyrosine Phosphatases in the context of their membrane bound receptor forms. This chapter aims to provide a current understanding of these proteins, in the background of their foundational past research.