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

Fingerprint

Oocytes
Ovum
Phosphotransferases
Embryonic Structures
Phosphorylation
Zygote
Phosphoric Monoester Hydrolases
Serine
Tyrosine
Cell Cycle
Chemical activation
Cells
Proteins

Keywords

  • DEVBIO
  • SIGNALING

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Regulation of MBK-2/DYRK by CDK-1 and the Pseudophosphatases EGG-4 and EGG-5 during the Oocyte-to-Embryo Transition. / Cheng, Ken Chih Chien; Klancer, Richard; Singson, Andrew; Seydoux, Geraldine.

In: Cell, Vol. 139, No. 3, 30.10.2009, p. 560-572.

Research output: Contribution to journalArticle

Cheng, Ken Chih Chien ; Klancer, Richard ; Singson, Andrew ; Seydoux, Geraldine. / Regulation of MBK-2/DYRK by CDK-1 and the Pseudophosphatases EGG-4 and EGG-5 during the Oocyte-to-Embryo Transition. In: Cell. 2009 ; Vol. 139, No. 3. pp. 560-572.
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