Coordinate regulation of the mother centriole component Nlp by Nek2 and Plk1 protein kinases
Coordinate regulation of the mother centriole component Nlp by Nek2 and Plk1 protein kinases
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DOI：
10.1128/mcb.25.4.1309-1324.2005
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发表时间：
2005-02-01
影响因子：
5.3
通讯作者：
Fry, AM
中科院分区：
文献类型：
--
作者：
Rapley, J;Baxter, JE;Fry, AM
有丝分裂进入需要微管细胞骨架的主要重组。Nip是一种结合γ-微管蛋白的中心体蛋白，是Plk 1蛋白激酶的G（2）/M靶点。在这里，我们表明，人类Nip和它的非洲爪蟾同源物，X-Nip，也被磷酸化的细胞周期调节Nek 2激酶。X-Nip是一种213 kDa的中心粒特异性蛋白，涉及微管锚定。虽然在整个细胞周期中丰度恒定，但在有丝分裂进入时从中心体移位。活性Nek 2或Plk 1的过表达导致Nip从间期中心体的过早移位。活性Nek 2还能够磷酸化和置换缺乏Plk 1磷酸化位点的Nlp突变形式。重要的是，激酶失活的Nek 2干扰Plk 1诱导的位移Nip从interpbase中心体和位移的内源性Nip从有丝分裂纺锤体极，而活性Nek 2刺激Plk 1磷酸化的Nip在体外。与Plk 1不同，Nek 2不阻止Nip与γ-微管蛋白的结合。总之，这些结果提供了参与微管组织的蛋白质的第一个例子，该蛋白质在G（2）/M转换时由两种中心体激酶协调调节。我们还建议，磷酸化的Nek 2可能总理Nlp磷酸化的Plk 1。
Mitotic entry requires a major reorganization of the microtubule cytoskeleton. Nip, a centrosomal protein that binds gamma-tubulin, is a G(2)/M target of the Plk1 protein kinase. Here, we show that human Nip and its Xenopus homologue, X-Nip, are also phosphorylated by the cell cycle-regulated Nek2 kinase. X-Nip is a 213-kDa mother centriole-specific protein, implicating it in microtubule anchoring. Although constant in abundance throughout the cell cycle, it is displaced from centrosomes upon mitotic entry. Overexpression of active Nek2 or Plk1 causes premature displacement of Nip from interphase centrosomes. Active Nek2 is also capable of phosphorylating and displacing a mutant form of Nlp that lacks Plk1 phosphorylation sites. Importantly, kinase-inactive Nek2 interferes with Plk1-induced displacement of Nip from interpbase centrosomes and displacement of endogenous Nip from mitotic spindle poles, while active Nek2 stimulates Plk1 phosphorylation of Nip in vitro. Unlike Plk1, Nek2 does not prevent association of Nip with gamma-tubulin. Together, these results provide the first example of a protein involved in microtubule organization that is coordinately regulated at the G(2)/M transition by two centrosomal kinases. We also propose that phosphorylation by Nek2 may prime Nlp for phosphorylation by Plk1.