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

被引：73

作者：

Cheng, Ken Chih-Chien ^{[1
,2
]}

Klancer, Richard ^{[3
,4
]}

Singson, Andrew ^{[3
,4
]}

Seydoux, Geraldine ^{[1
,2
]}

机构：

[1] Johns Hopkins Sch Med, Ctr Cell Dynam, Dept Mol Biol & Genet, Baltimore, MD 21205 USA

[2] Johns Hopkins Sch Med, Ctr Cell Dynam, Howard Hughes Med Inst, Baltimore, MD 21205 USA

[3] Rutgers State Univ, Waksman Inst, Piscataway, NJ 08854 USA

[4] Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA

来源：

CELL | 2009年 / 139卷 / 03期

基金：

美国国家卫生研究院;

关键词：

CYCLIN-DEPENDENT KINASE; C-ELEGANS; CAENORHABDITIS-ELEGANS; PROTEIN-KINASE; DUAL-SPECIFICITY; ACTIVATION; MATURATION; DYRK; DEGRADATION; OMA-1;

D O I：

10.1016/j.cell.2009.08.047

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-20s 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.

引用

页码：560 / 572

页数：13

共 41 条

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