Sidebar D. PP2C at a glance

PP2C is the unique member of the family of Mg2+/Mn2+-dependent protein phosphatases [126]. It is found in both eukaryotes and some prokaryotes. PP2C is monomeric with two structural domains, a conserved N-terminal catalytic domain and a C-terminal region with substantial structural and sequence variance among different isoforms. The residues and the folding pattern of the active-site are highly conserved among eukaryotes, with two central five-stranded β-sheets sandwiched by two pairs of α-helices. The catalytic site is located at the edge of the two central β-sheets and contains 3 atoms of either Mn2+ or Mg2+ ions. In metazoa, gene duplication has led to functional diversification through many isoforms of PP2C (18 in mammalian cells) that have gained specificity for various signalling pathways and tissue expression patterns. These isoforms have been implicated in the regulation of stress signalling cascades, phosphatidylinositol 3-kinase/Akt signalling, pre-mRNA splicing, protein ubiquitination and degradation as well as cell metabolism, highlighting the role of PP2C in controlling cell differentiation, proliferation, growth and survival/death. However, little is known about the regulatory mechanisms of PP2C at the molecular level. Special emphasis should be placed on plants, in which PP2C represents the major group of protein phosphatases and is at the center stage of the major signalling pathways controlled by abscisic acid and regulating plant responses to stresses as well as plant growth and development [127].