Fry A M, Meraldi P, Nigg E A
Department of Molecular Biology, Sciences II, University of Geneva, Switzerland.
EMBO J. 1998 Jan 15;17(2):470-81. doi: 10.1093/emboj/17.2.470.
Nek2, a mammalian protein kinase of unknown function, is closely related to the mitotic regulator NIMA of Aspergillus nidulans. Here we show by both immunofluorescence microscopy and biochemical fractionation that human Nek2 localizes to the centrosome. Centrosome association occurs throughout the cell cycle, including all stages of mitosis, and is independent of microtubules. Overexpression of active Nek2 induces a striking splitting of centrosomes, whereas prolonged expression of either active or inactive Nek2 leads to dispersal of centrosomal material and loss of a focused microtubule-nucleating activity. Surprisingly, this does not prevent entry into mitosis, as judged by the accumulation of mitotically arrested cells induced by co-expression of a non-destructible B-type cyclin. These results bear on the dynamic function of centrosomes at the onset of mitosis. Moreover, they indicate that one function of mammalian Nek2 relates to the centrosome cycle and thus provide a new perspective on the role of NIMA-related kinases.
Nek2是一种功能未知的哺乳动物蛋白激酶，与构巢曲霉的有丝分裂调节因子NIMA密切相关。我们通过免疫荧光显微镜和生化分级分离法表明，人类Nek2定位于中心体。中心体结合在整个细胞周期中都存在，包括有丝分裂的所有阶段，并且独立于微管。活性Nek2的过表达会导致中心体显著分裂，而活性或非活性Nek2的长时间表达会导致中心体物质分散以及聚焦的微管成核活性丧失。令人惊讶的是，这并不妨碍进入有丝分裂，这可通过共表达不可破坏的B型细胞周期蛋白诱导的有丝分裂停滞细胞的积累来判断。这些结果与有丝分裂开始时中心体的动态功能有关。此外，它们表明哺乳动物Nek2的一个功能与中心体周期有关，从而为NIMA相关激酶的作用提供了新的视角。
