Wee1B is an oocyte‐specific kinase involved in the control of meiotic arrest in the mouse

Abstract

In species ranging from sea urchin to human, the second messenger cAMP and activation of protein kinase A (PKA) plays a critical role in maintaining the oocyte meiotic arrest. However, the substrates phosphorylated by PKA in the oocyte, as well as the interface between cAMP signaling and meiosis promoting factor (MPF, cdc2/cyclin B complex), are largely unknown. Using small pool expression screening, we isolated several putative PKA substrates from a mouse oocyte library. One of these clones encodes a protein homologous to the Wee1 kinase, which phosphorylates and inactivates the cdc2/cyclin B complex during the interphase of the mitotic cycle. The isolated mWee1B is highly homologous to the Wee1A kinase expressed in Xenopus eggs and its overexpression blocks maturation induced by progesterone. Unlike the widely expressed Wee1 and Myt1, mWee1B mRNA and protein are expressed only in oocytes, and mRNA downregulation by RNAi injection in vitro, or transgenic overexpression of RNAi in vivo, causes a leaky meiotic arrest. Ser15 of mWee1B is the major PKA phosphorylation site in vitro, and the inhibitory effects of the kinase are enhanced when this residue is phosphorylated. Thus, mWee1B is a key MPF inhibitory kinase in mouse oocytes functioning downstream of PKA and is requisite for maintaining meiotic arrest. (Supported by U54-HD31398 and a grant from Organon)