Structural studies indicate that the PBD binds intramolecularly to its own kinase domain ( Elia et al.,2003b), inhibiting both kinase activity and the ability of PLK to bind phosphopeptides ( Elia et al.,2003b Jang et al.,2002 Lee and Erikson,1997 Mundt et al.,1997). The PBD binds preferentially to phosphorylated serine or threonine at the consensus sequence S-P/X ( Elia et al., 2003a), and is crucial for in vivo spatial and temporal subcellular localization of polo kinases( Lee et al., 1998 Lee et al., 1999 Qi et al., 2006 Seong et al., 2002). Both domains are essential for PLK function in vivo. All PLKs possess an N-terminal kinase domain and a noncatalytic, C-terminal polo box domain (PBD), composed of two related polo boxes, each approximately 70-80 residues long ( Clay et al.,1993 Lee et al.,1998). In addition, PLKs have also been shown to function in a number of other cell biological processes( Eckerdt et al., 2005 Ma et al., 2003 Seeburg et al., 2005 Takai et al., 2005 Wang et al., 2007). Polo and polo-like kinases (PLKs) are serine/threonine kinases that regulate diverse processes during cell division, including centrosomal duplication and maturation, DNA damage checkpoint activation, mitotic onset,bipolar spindle formation, Golgi fragmentation and assembly, chromosome segregation, and cytokinesis ( Glover et al., 1998 Nigg,1998). MEX-5/6 are themselves also substrates for this ZIF-1-containing E3 ligase complex ( DeRenzo et al.,2003). Both asymmetric distribution of PIE-1 before division, as well as asymmetric degradation after division, require the function of MEX-5/6( DeRenzo et al., 2003 Schubert et al., 2000). The small amount of PIE-1 segregated to the somatic sister after each division is degraded by a ZIF-1-containing CUL-2 E3 ligase complex ( DeRenzo et al.,2003 Reese et al.,2000). After cell division, PIE-1 is enriched in P1, and this pattern reiterates in each subsequent P-lineage division. In the one-cell embryo, as MEX-5/6 become asymmetrically localized anteriorly, PIE-1 becomes localized posteriorly( Cuenca et al., 2003 Mello et al., 1996 Schubert et al., 2000). One major function of MEX-5/6 is to restrict the localization of maternally supplied germline proteins, such as PIE-1, POS-1 and MEX-1, to germline blastomeres ( Guedes and Priess,1997 Mello et al.,1996 Schubert et al.,2000 Tabara et al.,1999). Our results provide a mechanism by which MEX-5 and MEX-6 function is temporally regulated during the crucial oocyte-to-embryo transition. Prior phosphorylation of MEX-5 at T 186 greatly enhances phosphorylation of MEX-5 by polo kinases in vitro. We also show that MBK-2, a developmentally regulated DYRK2 kinase activated at meiosis II,primes T 186 for subsequent polo kinase-dependent phosphorylation. We identify an amino acid of MEX-5, T 186, essential for polo binding and show that T 186 is important for MEX-5 function in vivo. This asymmetric localization of polo kinases depends on MEX-5 and MEX-6, as well as genes regulating MEX-5 and MEX-6 asymmetry. elegans embryos in a pattern identical to that of MEX-5 and MEX-6. These polo kinases are asymmetrically localized along the anteroposterior axis of newly fertilized C. We show that polo kinases, via their polo box domains, bind to and regulate the activity of two key polarity proteins, MEX-5 and MEX-6. Here we report a novel, non-cell division function for polo kinases in embryonic polarity of newly fertilized Caenorhabditis elegans embryos. Polo kinases are known key regulators of cell divisions.
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