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

摘要

DYRKs are kinases that self-activate in vitro by auto-phosphorylation 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 pseudo-tyrosine 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 novel 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.