Sidebar B. PP1 at a glance

PP1 is a multimeric complex composed of one catalytic subunit (PP1c) associated to one or two regulatory proteins, called PIPs (PP1-interacting proteins). In vertebrates, PP1c is expressed as four distinct isoforms: PP1α, β, γ1 and γ2, the latter one being specific of testis. In eukaryotes, more than 200 PIPs have been described to date and these proteins regulate substrate specificity and cell localization of PP1c. Some of them act as direct regulators of PP1 activity while others, either specify its subcellular localization or behave as pseudo-substrates to inhibit PP1 activity [75–77]. PIPs interact with PP1c through well-characterized domains, the SLiMs (short linear motifs). In particular, 85% of PIPs share one main binding motif corresponding to the RVXF consensus sequence, in which X represents any amino acid except proline [78]. Besides its regulation by PIPs, PP1c activity is directly inhibited by phosphorylation at T320 within its catalytic domain [79–81]. This residue is dephosphorylated by PP1c itself and phosphorylated by Cdk1 and Cdk2 during the cell cycle.