Regulation of protein phosphatases in disease and behaviour

Abstract

The EMBO conference/FEBS advanced course on phosphatases, ‘EuroPhosphatases 2003’, was held in Barcelona, Spain, between 29 June and 3 July 2003, and was organized by J. Arino and D. Alexander. ![][1] The biennial EuroPhosphatases meeting was held near the Sagrada Familia, Antonio Gaudi's unfinished architectural masterpiece, which could be a metaphor for the phosphatase field: a lot has been achieved, but much more work still needs to be done. Protein phosphorylation is reversible and has a regulatory role in many—if not all—biological processes. The enzymes involved in protein dephosphorylation, the protein phosphatases (PPs), are classified on the basis of their substrate specificity into serine/threonine PPs, protein‐tyrosine phosphatases (PTPs) and protein‐histidine phosphatases (PHPs). Molecular cloning has indicated that these three classes belong to four gene families, two of which, the PPP and the PPM family, encode the Ser/Thr PPs (Barford, 1996). The Ser/Thr PPs consist of a single catalytic subunit and one or more regulatory subunits. The large family of PTPs consists of classical PTPs with substrate specificity for phosphotyrosine (pTyr), dual‐specificity phosphatases (DSPs) that dephosphorylate pSer, pThr and pTyr, and lipid phosphatases (Tonks & Neel, 2001). Finally, little is known about histidine phosphorylation in vertebrates. S. Klumpp (Munster, Germany) described the purification and cloning of the only known mammalian PHP, PHP1, which is not homologous to any other PP (Klumpp & Krieglstein, 2002). The general view of dynamic cell signalling through phosphorylation is changing. D. Brautigan (Charlottesville, VA, USA) argued that PP activity should no longer be considered to be at a constant, low level, but rather that a relatively high level of PP activity keeps the cell in check until a stimulus tips the protein kinase (PK)/PP balance through the simultaneous activation of PKs and the inactivation of PPs (Fig. 1). This model implies that PPs are tightly regulated. … [1]: /embed/graphic-1.gif