Nishi Yuichi, Rogers Eric, Robertson Scott M, Lin Rueyling
Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Development. 2008 Feb;135(4):687-97. doi: 10.1242/dev.013425. Epub 2008 Jan 16.
Polo kinases are known key regulators of cell divisions. Here we report a novel, non-cell division function for polo kinases in embryonic polarity of newly fertilized Caenorhabditis elegans embryos. 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. These polo kinases are asymmetrically localized along the anteroposterior axis of newly fertilized C. elegans embryos in a pattern identical to that of MEX-5 and MEX-6. This asymmetric localization of polo kinases depends on MEX-5 and MEX-6, as well as genes regulating MEX-5 and MEX-6 asymmetry. 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. We also show that MBK-2, a developmentally regulated DYRK2 kinase activated at meiosis II, primes T(186) for subsequent polo kinase-dependent phosphorylation. Prior phosphorylation of MEX-5 at T(186) greatly enhances phosphorylation of MEX-5 by polo kinases in vitro. Our results provide a mechanism by which MEX-5 and MEX-6 function is temporally regulated during the crucial oocyte-to-embryo transition.
Polo激酶是已知的细胞分裂关键调节因子。在此，我们报道了Polo激酶在新受精的秀丽隐杆线虫胚胎的胚胎极性中具有一种新的非细胞分裂功能。我们发现，Polo激酶通过其Polo框结构域，结合并调节两种关键极性蛋白MEX - 5和MEX - 6的活性。这些Polo激酶沿着新受精的秀丽隐杆线虫胚胎的前后轴不对称定位，其模式与MEX - 5和MEX - 6相同。Polo激酶的这种不对称定位依赖于MEX - 5和MEX - 6，以及调节MEX - 5和MEX - 6不对称性的基因。我们鉴定出MEX - 5的一个氨基酸T(186)，它对于与Polo结合至关重要，并表明T(186)在体内对MEX - 5的功能很重要。我们还表明，MBK - 2是一种在减数分裂II期被激活的受发育调控的DYRK2激酶，它使T(186)磷酸化，以便随后依赖Polo激酶的磷酸化。MEX - 。我们的结果提供了一种机制，通过该机制，在关键的卵母细胞到胚胎的转变过程中，MEX - 5和MEX - 6的功能在时间上受到调节。 5在T(186)处的预先磷酸化在体外极大地增强了Polo激酶对MEX - 5的磷酸化作用。
