Protein Phosphatases

The dephosphorylation of proteins is catalyzed by enzymes known as protein phosphatases, which act to reverse the actions of protein kinases. On the one hand, protein phosphatases are less attractive drug targets, because they typically act on a broader range of proteins than kinases do. With over 500,000 human phosphorylation sites, each phosphatase would target on average over 3500 phospho-sites. On the one hand, inhibitors of certain protein phosphatases (e.g. okadaic acid, microcysteines, teleocidins) are known to be extremely potent tumour promoters. Many of these are naturally occurring toxins that for example contaminate drinking water and shellfish that produce illness.

Consequently, phosphatases can become important sentinels of unhealthy environmental conditions. On the other hand, there are likely to be many diseases distinct from cancer, where a gain of specific phosphatase function may contribute to the pathology. In such instances, these phosphatases may serve as appropriate drug targets.

From analysis of human genome databases, Kinexus has determined that there are at least 138 protein phosphatases (34 dual specificity phosphatases, 14 phosphatidyl-inositol-phosphate phosphatase-related phosphatases, 41 protein-serine/threonine phosphatases, 22 receptor-tyrosine phosphatases, and 27 non-receptor-tyrosine phosphatases).