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PMID: 19879842 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Cell ·Vol. 139 ·No. 3 ·2009-10-30 ·Pages 560-72

Cheng KC, Klancer R, Singson A, Seydoux G

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.

MeSH Terms
Animals CDC2 Protein Kinase/metabolism Caenorhabditis elegans/embryology,metabolism Caenorhabditis elegans Proteins/metabolism Embryo, Nonmammalian/metabolism Humans Oocytes/metabolism Protein-Tyrosine Kinases/metabolism
Chemicals
Caenorhabditis elegans Proteins EGG-4 protein, C elegans EGG-5 protein, C elegans MBK-2 protein, C elegans Protein-Tyrosine Kinases CDC2 Protein Kinase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cheng Ken Chih-Chien
Department of Molecular Biology and Genetics and Howard Hughes Medical Institute, Center for Cell Dynamics, Johns Hopkins School of Medicine, 725 N. Wolfe Street, PCTB 706, Baltimore, MD 21205, USA.
Klancer Richard
Singson Andrew
Seydoux Geraldine
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2009.08.047
Published
2009-10-30
Pages
560-72
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2790168
Subset
IM
Grants
NICHD NIH HHS · R01 HD037047 · United States
NICHD NIH HHS · R01 HD037047-10 · United States
NICHD NIH HHS · R01 HD054681 · United States
NICHD NIH HHS · R01HD054681 · United States
Howard Hughes Medical Institute · United States
NICHD NIH HHS · R01HD37047 · United States
Corrections
CommentIn
PMID: 19879835
External Links
PubMed source DOI: 10.1016/j.cell.2009.08.047 PMC Full Text View journal details
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