Protein Tyrosine Phosphatases

The process of reversible phosphorylation is perhaps the cell's most prevalent means of regulation at the molecular level. It has been estimated that up to 30% of all cellular proteins are phosphorylated, and phosphorylation has been shown to play a crucial regulatory role in such diverse cellular events as metabolism, growth and differentiation, vesicular transport, and gene transcription. Phosphorylation and dephosphorylation are carried out by kinases and phosphatases, respectively. There are currently predicted to be 518 kinases and ~125 phosphatases encoded in the human genome, further underscoring the overall importance of phosphorylation in molecular regulation. Phosphatases are generally divided into two main families based on their catalytic mechanism and substrate specificity: the protein phosphatases (PPs), which exclusively desphosphorylate serine and threonine residues, and the protein tyrosine phosphatases (PTPs), which can dephosphorylate tyrosine residues, and are the focus of this article. PTPs can be further classified into subfamilies based on (1) subcellular location (receptor vs. intracellular), (2) substrate preference, and (3) three-dimensional topology. In this article, we describe the different subfamilies of PTPs and their conserved catalytic mechanism. In addition, we briefly discuss human diseases that result from disrupted PTP signaling, and discuss the pursuit of PTPs as drug targets.