The M-phase regulatory phosphatase PP2A-B55δ opposes protein kinase A on Arpp19 to initiate meiotic division

Abstract

Oocytes are held in meiotic prophase for prolonged periods until hormonal signals trigger meiotic divisions. Key players of M-phase entry are the opposing Cdk1 kinase and PP2A-B55{delta} phosphatase. In Xenopus, the protein Arpp19, phosphorylated at serine 67 by Greatwall, plays an essential role in inhibiting PP2A-B55{delta}, promoting Cdk1 activation. Furthermore Arpp19 has an earlier role in maintaining the prophase arrest through a second serine (S109) phosphorylated by PKA. Prophase release, induced by progesterone, relies on Arpp19 dephosphorylation at S109, owing to an unknown phosphatase. Here we identified this phosphatase as PP2A-B55{delta}. In prophase, PKA and PP2A-B55{delta} are simultaneously active, suggesting the presence of other important targets for both enzymes. The drop in PKA activity induced by progesterone decreases S109 phosphorylation, unlocking the prophase block. Hence, PP2A-B55{delta} acts critically on Arpp19 on two distinct sites, opposing PKA and Greatwall to orchestrate the prophase release and M-phase entry.