Protein phosphorylation and protein phosphatases. De Panne, Belgium, September 19-24, 1999.

Abstract

About one‐third of all proteins in eukaryotic cells are thought to be phosphorylated at any one time. An understanding of how a particular cellular process is regulated by protein phosphorylation requires an insight into (i) the identity of the phosphoproteins and their phosphorylation sites, (ii) the effects of their phosphorylation, (iii) the nature of the protein kinases (PKs) and protein phosphatases (PPs) involved, and (iv) the mechanisms that determine when and where these enzymes are active. The dynamic nature of protein phosphorylation implies that phosphorylation levels can be modulated by changes in the activities of either PKs or PPs. These enzymes show a great structural diversity, and their activities are tightly regulated by hormones, growth factors and metabolites. The recent progress in our understanding of the structure and regulation of protein phosphatases and of their role in various cellular processes was the subject of an EMBO conference that was organized in De Panne, Belgium (September 19–24, 1999) by M.Bollen, D.Barford and S.Klumpp. This ‘Europhosphatase’ conference attracted 170 participants from 25 different countries. Protein phosphatases are classified into three families, based on the structure of their catalytic domains. The PPP family includes the phosphoserine/phosphothreonine‐specific protein phosphatases PP1, PP2A, PP2B (calcineurin), PP4 and PP5. The PPM family comprises Mg2+‐stimulated protein phosphatases, such as PP2C, which also dephosphorylate phosphoserine and phosphothreonine residues. Protein‐tyrosine phosphatases and ‘dual‐specificity’ protein phosphatases, which dephosphorylate all three phosphoamino acids, belong to the PTP family. S.Klumpp (Marburg, Germany) reported on the purification of a histidine phosphatase from rat liver (14 kDa) that is insensitive to classical phosphatase inhibitors except Pi. Peptide sequencing did not show any homology with known protein phosphatases. This enzyme is therefore likely to represent the first member of a new family, putatively termed PHP for protein‐histidine phosphatases. The genome of Saccharomyces …