Differential control of the NIMA-related kinases, Nek6 and Nek7, by serum stimulation
Differential control of the NIMA-related kinases, Nek6 and Nek7, by serum stimulation
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DOI：
10.1016/s0006-291x(03)00049-4
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发表时间：
2003-02-21
影响因子：
3.1
通讯作者：
Yoshimura, A
中科院分区：
文献类型：
--
作者：
Minoguchi, S;Minoguchi, M;Yoshimura, A
Neks（NIMA相关激酶）是哺乳动物丝氨酸/苏氨酸（Ser/Thr）蛋白激酶，结构上与曲霉NIMA（有丝分裂中的Never，基因A）相关，其在有丝分裂信号传导中起重要作用。在这些激酶中，Nek 6和Nek 7在结构上相关，并构成NIMA/Nek家族的一个亚家族，尽管它们的功能仍然几乎难以捉摸。在这份报告中，我们研究了Nek 6和Nek 7的酶促调节，以深入了解它们的细胞功能。在细菌中产生的重组Nek 7与Nek 6相比具有活性;然而，发现Nek 7在哺乳动物细胞中的活性显著低于Nek 6。由于Nek 6先前已被报道在Thr 412处体外磷酸化p70核糖体S6激酶，我们检查了Nek 6和Nek 7活性是否受氨基酸补充剂控制，已知其影响Thr 412处的磷酸化，并且没有观察到任何显著影响。然而，我们意外地发现，Nek 7激酶活性通过血清剥夺快速有效地增加，而Nek 6活性降低。这与正常生长条件下细胞中Nek 7的较低活性完全一致。此外，有人建议，Nek 7的活性将在细胞周期依赖性的方式进行调节，虽然Nek 6不是。高度相似的激酶Nek 6和Nek 7之间在酶控制方面的这些明显差异表明它们在哺乳动物细胞中具有不同的信号传导功能。(C)2003 Elsevier Science（美国）。All rights reserved.
Neks (NIMA-related kinases) are mammalian serine/threonine (Ser/Thr) protein kinases structurally related to Aspergillus NIMA (Never in Mitosis, gene A), which plays essential roles in mitotic signaling. Among these kinases, Nek6 and Nek7 are structurally related and constitute a subfamily in the NIMA/Nek family, although their functions still remain almost elusive. In this report, we studied the enzymatic regulation of Nek6 and Nek7 to gain an insight into their cellular functions. Recombinant Nek7 produced in bacteria was active comparably to Nek6; however, the Nek7 activity in-mammalian cells was found to be significantly lower than Nek6. Since Nek6 previously has been reported to in vitro phosphorylate p70 ribosomal S6 kinase at Thr412, we examined if Nek6 and Nek7 activities were controlled by the amino acid supplement, which is known to affect the phosphorylation at Thr412, and did not observe any significant effect. However, we unexpectedly found that Nek7 kinase activity was rapidly and efficiently increased by serum deprivation, while Nek6 activity was decreased. This is well consistent with the lower activity of Nek7 in cells under normal growth conditions. In addition, it was suggested that Nek7 activity would be regulated in a cell cycle-dependent manner, although Nek6 was not. These clear differences in enzymatic control between the highly similar kinases, Nek6 and Nek7, suggest their distinct signaling functions in mammalian cells. (C) 2003 Elsevier Science (USA). All rights reserved.