Regulation of MBK-2/DYRK by CDK-1 and the Pseudophosphatases EGG-4 and EGG-5 during the Oocyte-to-Embryo Transition

Ken Chih Chien Cheng, Richard Klancer, Andrew Singson, Geraldine Seydoux

Research output: Contribution to journalArticle

Abstract

DYRKs are kinases that self-activate in vitro by autophosphorylation of a YTY motif in the kinase domain, but their regulation in vivo is not well understood. In C. elegans zygotes, MBK-2/DYRK phosphorylates oocyte proteins at the end of the meiotic divisions to promote the oocyte-to-embryo transition. Here we demonstrate that MBK-2 is under both positive and negative regulation during the transition. MBK-2 is activated during oocyte maturation by CDK-1-dependent phosphorylation of serine 68, a residue outside of the kinase domain required for full activity in vivo. The pseudotyrosine phosphatases EGG-4 and EGG-5 sequester activated MBK-2 until the meiotic divisions by binding to the YTY motif and inhibiting MBK-2′s kinase activity directly, using a mixed-inhibition mechanism that does not involve tyrosine dephosphorylation. Our findings link cell-cycle progression to MBK-2/DYRK activation and the oocyte-to-embryo transition.

Original languageEnglish (US)
Pages (from-to)560-572
Number of pages13
JournalCell
Volume139
Issue number3
DOIs
StatePublished - Oct 30 2009
Externally publishedYes

Keywords

  • DEVBIO
  • SIGNALING

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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