Regulation of MBK-2/DYRK by CDK-1 and the pseudophosphatases EGG-4 and EGG-5 during the oocyte-to-embryo transition

Cell. 2009 Oct 30;139(3):560-72. doi: 10.1016/j.cell.2009.08.047.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CDC2 Protein Kinase / metabolism*
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism*
  • Embryo, Nonmammalian / metabolism
  • Humans
  • Oocytes / metabolism
  • Protein-Tyrosine Kinases / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • EGG-4 protein, C elegans
  • EGG-5 protein, C elegans
  • MBK-2 protein, C elegans
  • Protein-Tyrosine Kinases
  • CDC2 Protein Kinase