Sidebar C. PP2A at a glance

PP2A is a heterotrimer composed of a catalytic subunit (PP2A-C), a structural subunit (PP2A-A) and a regulatory subunit (PP2A-B). Eukaryotes have four B-subunit families known as B/B55 (PR55), B′/B56 (PR61), B″/B72 and B‴/Striatin, each of them comprising several very close isoforms whose number differs according the species [91]. Some of these different isoforms are specific to vertebrates, in particular the four α, β, γ and δ isoforms of B55 and the 5 isoforms α, β, γ, δ and ε of B56 [92]. The core part of PP2A is formed by the dimer PP2A-A/C and its association to a regulatory B-subunit drives both its substrate specificity and intracellular localization. Because of the multiple isoforms of PP2A subunits, hundreds of different holoenzymes are potentially generated that display very similar catalytic domains. Several mechanisms allow for the specific recognition of substrates by PP2A holoenzymes in vivo. Substrate binding involves specific consensus motifs: PP2A-B56 recognizes the SLiM “LxxIxE” while PP2A-B55 preferentially targets substrates with positively charged polybasic units on either side of the residue to be dephosphorylated [93–95]. Furthermore, phosphorylation of residues inside or adjacent to PP2A-B56 recognition motifs potentiates its binding to the substrate [94, 96].