Cell cycle-dependent expression and centrosome localization of a third human Aurora/Ip11-related protein kinase, AIK3
Cell cycle-dependent expression and centrosome localization of a third human Aurora/Ip11-related protein kinase, AIK3
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DOI：
10.1074/jbc.274.11.7334
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发表时间：
1999-03-12
影响因子：
4.8
通讯作者：
Okano, Y
中科院分区：
文献类型：
--
作者：
Kimura, M;Matsuda, Y;Okano, Y
我们早些时候分离到了编码新的人类蛋白激酶AIk和AIK2的cDNA，它们与果蝇Aurora和酿酒酵母Ipl1激酶具有高度氨基酸序列同源性，它们的突变会导致染色体异常分离。在本研究中，我们分离到了与artrora/Ipl1高度同源的第三个人c DNA(AIK3)，并测定了其核苷酸序列。该基因编码309个氨基酸，预测分子质量为35.9 kDa。AIK3蛋白的C端结构域与人AIK、人AIK2、非洲爪哇pEg2、果蝇Aurora和酵母Ipl1等Aurora/Ipl1家族蛋白激酶的氨基酸序列高度同源，而与其他Aurora/Ipl1家族成员的同源性较低。通过荧光原位杂交、体细胞杂交板和辐射杂交板，将AIK3基因定位于人染色体19q13.43，该区域是多种肿瘤组织中常见的缺失或重排区域。Northern印迹分析表明，AIK3仅在睾丸中表达，与正常成纤维细胞相比，AIK3在几个癌细胞系中的表达水平升高了数倍。在HeLa细胞中，内源性AIK3蛋白水平在G(1)/S中较低，在G(2)/M期积累，有丝分裂后减少。免疫荧光研究表明，在有丝分裂后期到胞质分裂过程中，AIK3定位于中心体。这些结果表明，AIK3可能在有丝分裂后期的中心体功能中发挥作用(S)。
We earlier isolated cDNAs encoding novel human protein kinases AIK and AIK2 sharing high amino acid sequence identities with Drosophila Aurora and Saccharomyces cerevisiae Ipl1 kinases whose mutations cause abnormal chromosome segregation. In the present study, a third human cDNA (AIK3) highly homologous to artrora/IPL1 was isolated, and the nucleotide sequence was determined. This cDNA encodes 309 amino acids with a predicted molecular mass of 35.9 kDa, C-terminal kinase domain of AIK3 protein shares high amino acid sequence identities with those of Aurora/Ipl1 family protein kinases including human AIK, human AIK2, Xenopus pEg2, Drosophila Aurora, and yeast Ipl1, whereas the N-terminal domain of AIK3 protein shares little homology with any other Aurora/Ipl1 family members. AIK3 gene was assigned to human chromosome 19q13.43, which is a frequently deleted or rearranged region in several tumor tissues, by fluorescence in situ hybridization, somatic cell hybrid panel, and radiation hybrid cell panel. Northern blot analyses revealed that AIK3 expression was limited to testis, The expression levels of AIK3 in several cancer cell lines were elevated severalfold compared with normal fibroblasts. In HeLa cells, the endogenous AIK3 protein level is low in G(1)/S, accumulates during G(2)/M, and reduces after mitosis, Immunofluorescence studies using a specific antibody have shown that AIK3 is localized to centrosome during mitosis from anaphase to cytokinesis, These results suggest that AIK3 may play a role(s) in centrosome function at later stages of mitosis.