Title: Wee1B Is an Oocyte-Specific Kinase Involved in the Control of Meiotic Arrest in the Mouse
Abstract: In most species, the meiotic cell cycle is arrested at the transition between prophase and metaphase through unclear somatic signals. Activation of the Cdc2-kinase component of maturation promoting factor (MPF) triggers germinal vesicle breakdown after the luteinizing hormone (LH) surge and reentry into the meiotic cell cycle [1Tsafriri A. Dekel N. Molecular mechanisms in ovulation.in: Findlay J.K. Molecular Biology of the Female Reproductive System. Academic Press, San Diego1994: 207-258Crossref Google Scholar, 2Eppig J.J. Regulation of mammalian oocyte maturation.in: Adashi E.Y. Leung P.C.K. The Ovary. Raven Press, Ltd, New York1993: 185-208Google Scholar, 3Dekel N. Protein phosphorylation/dephosphorylation in the meiotic cell cycle of mammalian oocytes.Rev. Reprod. 1996; 1: 82-88Crossref PubMed Scopus (58) Google Scholar]. Although high levels of cAMP and activation of protein kinase A (PKA) play a critical role in maintaining an inactive Cdc2 [4Maller J.L. Krebs E.G. Progesterone-stimulated meiotic cell division in Xenopus oocytes. Induction by regulatory subunit and inhibition by catalytic subunit of adenosine 3′:5′-monophosphate-dependent protein kinase.J. Biol. Chem. 1977; 252: 1712-1718Abstract Full Text PDF PubMed Google Scholar, 5Bornslaeger E.A. Mattei P. Schultz R.M. Involvement of cAMP-dependent protein kinase and protein phosphorylation in regulation of mouse oocyte maturation.Dev. Biol. 1986; 114: 453-462Crossref PubMed Scopus (201) Google Scholar, 6Conti M. Andersen C.B. Richard F.J. Shitsukawa K. Tsafriri A. Role of cyclic nucleotide phosphodiesterases in resumption of meiosis.Mol. Cell. Endocrinol. 1998; 145: 9-14Crossref PubMed Scopus (68) Google Scholar], the steps downstream of PKA in the oocyte remain unknown. Using a small-pool expression-screening strategy, we have isolated several putative PKA substrates from a mouse oocyte cDNA library. One of these clones encodes a Wee1-like kinase that prevents progesterone-induced oocyte maturation when expressed in Xenopus oocytes. Unlike the widely expressed Wee1 and Myt1, mWee1B mRNA and its 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 residue 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, functions downstream of PKA, and is required for maintaining meiotic arrest.