Protein tyrosine kinase Wee1B is essential for metaphase II exit in mouse oocytes

Science. 2011 Apr 22;332(6028):462-5. doi: 10.1126/science.1199211. Epub 2011 Mar 31.


Waves of cyclin synthesis and degradation regulate the activity of Cdc2 protein kinase during the cell cycle. Cdc2 inactivation by Wee1B-mediated phosphorylation is necessary for arrest of the oocyte at G2-prophase, but it is unclear whether this regulation functions later during the metaphase-to-anaphase transition. We show that reactivation of a Wee1B pathway triggers the decrease in Cdc2 activity during egg activation. When Wee1B is down-regulated, oocytes fail to form a pronucleus in response to Ca(2+) signals. Calcium-calmodulin-dependent kinase II (CaMKII) activates Wee1B, and CaMKII-driven exit from metaphase II is inhibited by Wee1B down-regulation, demonstrating that exit from metaphase requires not only a proteolytic degradation of cyclin B but also the inhibitory phosphorylation of Cdc2 by Wee1B.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CDC2 Protein Kinase / antagonists & inhibitors
  • CDC2 Protein Kinase / metabolism
  • Calcium / metabolism
  • Calcium Signaling
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cyclin B / genetics
  • Cyclin B / metabolism
  • Down-Regulation
  • Female
  • Gene Knockdown Techniques
  • Maturation-Promoting Factor / metabolism
  • Meiosis*
  • Metaphase*
  • Mice
  • Mice, Inbred C57BL
  • Oocytes / physiology*
  • Phosphorylation
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Cell Cycle Proteins
  • Cyclin B
  • RNA, Messenger
  • Wee1B protein, mouse
  • Protein-Tyrosine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • CDC2 Protein Kinase
  • Maturation-Promoting Factor
  • Calcium