Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
Mol Cell Biol. 2011 Jan;31(1):30-42. doi: 10.1128/MCB.00648-10. Epub 2010 Oct 18.
Appropriate cell cycle checkpoint control is essential for the maintenance of cell and organismal homeostasis. Members of the Nek (NIMA-related kinase) family of serine/threonine protein kinases have been implicated in the regulation of various aspects of the cell cycle. We explored the cellular functions of Nek10, a novel member of the Nek family, and demonstrate a role for Nek10 in the cellular UV response. Nek10 was required for the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling upon UV irradiation but not in response to mitogens, such as epidermal growth factor stimulation. Nek10 physically associated with Raf-1 and MEK1 in a Raf-1-dependent manner, and the formation of this complex was necessary for Nek10-mediated MEK1 activation. Nek10 did not affect the kinase activity of Raf-1 but instead promoted the autophosphorylation-dependent activation of MEK1. The appropriate maintenance of the G(2)/M checkpoint following UV irradiation required Nek10 expression and ERK1/2 activation. Taken together, our results uncover a role for Nek10 in the cellular response to UV irradiation.
适当的细胞周期检查点控制对于维持细胞和机体的内稳态至关重要。丝氨酸/苏氨酸蛋白激酶 Nek（NIMA 相关激酶）家族的成员参与了细胞周期的各个方面的调节。我们研究了 Nek 家族的新成员 Nek10 的细胞功能，并证明了 Nek10 在细胞对 UV 反应中的作用。在 UV 照射下，Nek10 对于细胞外信号调节激酶 1/2（ERK1/2）信号的激活是必需的，但对丝裂原（如表皮生长因子刺激）的反应则不是必需的。Nek10 以 Raf-1 依赖性方式与 Raf-1 和 MEK1 物理结合，并且该复合物的形成对于 Nek10 介导的 MEK1 激活是必需的。Nek10 不影响 Raf-1 的激酶活性，而是促进 MEK1 的依赖于自身磷酸化的激活。在 UV 照射后，适当维持 G（2）/M 检查点需要 Nek10 表达和 ERK1/2 激活。总之，我们的结果揭示了 Nek10 在细胞对 UV 照射反应中的作用。
