This is a growing web resource about a class of important enzymes called:

Protein Tyrosine Phosphatases (PTPs)

PTPs are a group of phosphatases that is classified as such by their common signature motif C(X)5R, including the catalytic cystein and the invariant arginine with 5 amino acid residues in between. The human genome contains at least 107 PTP genes with 81 encoding for active protein phosphatases [1]. Although called protein tyrosine phosphatases, only 38 members of the PTP family, the so-called classical PTPs, are tyrosine specific. A large group of 63 proteins belongs to the dual-specific PTPs, which can also catalyze dephosphorylation of serine/threonine, RNA, or even innositol.

Tyrosine Phosphorylation

Phosphorylation on tyrosine [2] is a rapidly reversible post-translational modification catalyzed by protein tyrosine kinases (PTKs) and reversed by PTPs, and plays a crucial role in many processes that are characteristic of higher eukaryotes. For instance, signal transduction processes are often regulated by phosphorylation cascades, which snow ball effect-like enhance and route signals from receptors located in the cell membrane to the genetic machinery in the nucleus of the cell, resulting in the production of specific proteins. Thereby, PTKs and PTPs are highly regulated to maintain this dynamic balance between phosphorylated and dephosphorylated state of a signaling molecule. Any disturbance of this balance, e.g. due to abnormal catalytic activity or altered expression levels of PTKs or PTPs, can lead to abnormal cell behavior and consequently to serious illnesses [3].

PTPs and cancer.

Disturbances of PTP function have been implicated in diverse human diseases including cancer [3,4,5]. This is best exemplified by the common loss of PTEN in many malignancies including glioblastomas, breast and prostate cancer, lymphomas, and other [6]. The finding that PTPs can also be overexpressed in cancer cells, illustrates the growing notion that PTPs not only act as tumor suppressors but also as ‘positive’ components of signaling pathways and cell functions. It appears that many cellular processes, such as cell motility, require a dynamic balance between kinases and phosphatases. Shp2 is the first family member to be recognized as a true oncogene, with various gain-of-function mutants occurring in several forms of leukemia [7]. Moreover, one of the best-characterized tyrosine phosphatases, PTP1B, has recently found to be a positive regulator of ErbB2 (HER2, P185^neu) induced signals that trigger tumorigenesis and metastasis [8,9]. Accordingly, PTP1B and other PTPs have been suggested as potential drug targets [3,4,5].