Serine/threonine-protein kinase Nek2

Definition:

Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly. NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis. Involved in the regulation of centrosome disjunction. Phosphorylates CCDC102B either directly or indirectly which causes CCDC102B to dissociate from the centrosome and allows for centrosome separation.; [Isoform 1]: Phosphorylates and activates NEK11 in G1/S-arrested cells.; [Isoform 2]: Not present in the nucleolus and, in contrast to isoform 1, does not phosphorylate and activate NEK11 in G1/S-arrested cells.

References:

[1]. Xiaohui Man, et al. Cep68 can be regulated by Nek2 and SCF complex. Eur J Cell Biol. 2015 Mar-Apr;94(3-4):162-72. [Content Brief]

[2]. Jun Mi, et al. Protein phosphatase-1alpha regulates centrosome splitting through Nek2. Cancer Res. 2007 Feb 1;67(3):1082-9. [Content Brief]

[3]. Yang Lou, et al. Nek2A specifies the centrosomal localization of Erk2. Biochem Biophys Res Commun. 2004 Aug 20;321(2):495-501. [Content Brief]

[4]. Shirin Bahmanyar, et al. beta-Catenin is a Nek2 substrate involved in centrosome separation. Genes Dev. 2008 Jan 1;22(1):91-105. [Content Brief]

[5]. Kohji Noguchi, et al. Nucleolar Nek11 is a novel target of Nek2A in G1/S-arrested cells. J Biol Chem. 2004 Jul 30;279(31):32716-27. [Content Brief]

[6]. Yuqing Xia, et al. CCDC102B functions in centrosome linker assembly and centrosome cohesion. J Cell Sci. 2018 Dec 3;131(23):jcs222901. [Content Brief]

[7]. Jianhui Yao, et al. Nek2A kinase regulates the localization of numatrin to centrosome in mitosis. FEBS Lett. 2004 Sep 24;575(1-3):112-8. [Content Brief]

[8]. J Du, et al. The mitotic checkpoint kinase NEK2A regulates kinetochore microtubule attachment stability. Oncogene. 2008 Jul 3;27(29):4107-14. [Content Brief]

[9]. Guosheng Fu, et al. Phosphorylation of human Sgo1 by NEK2A is essential for chromosome congression in mitosis. Cell Res. 2007 Jul;17(7):608-18. [Content Brief]

[10]. Wenjuan Wu, et al. Alternative splicing controls nuclear translocation of the cell cycle-regulated Nek2 kinase. J Biol Chem. 2007 Sep 7;282(36):26431-40. [Content Brief]

[11]. Guoliang Fang, et al. Centlein mediates an interaction between C-Nap1 and Cep68 to maintain centrosome cohesion. J Cell Sci. 2014 Apr 15;127(Pt 8):1631-9. [Content Brief]

[12]. Qingdu Liu, et al. Nek2 targets the mitotic checkpoint proteins Mad2 and Cdc20: a mechanism for aneuploidy in cancer. Exp Mol Pathol. 2010 Apr;88(2):225-33. [Content Brief]

[13]. Balca R Mardin, et al. Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nat Cell Biol. 2010 Dec;12(12):1166-76. [Content Brief]

[14]. Yang Lou, et al. NEK2A interacts with MAD1 and possibly functions as a novel integrator of the spindle checkpoint signaling. J Biol Chem. 2004 May 7;279(19):20049-57. [Content Brief]

[15]. Alison J Faragher, et al. Nek2A kinase stimulates centrosome disjunction and is required for formation of bipolar mitotic spindles. Mol Biol Cell. 2003 Jul;14(7):2876-89. [Content Brief]

[16]. Canhe Chen, et al. Characterization of Cep85 - a new antagonist of Nek2A that is involved in the regulation of centrosome disjunction. J Cell Sci. 2015 Sep 1;128(17):3290-303. [Content Brief]

[17]. Rebecca S Hames, et al. Alternative splice variants of the human centrosome kinase Nek2 exhibit distinct patterns of expression in mitosis. Biochem J. 2002 Jan 1;361(Pt 1):77-85. [Content Brief]

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