Molecular Neuroscience, Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo, Japan.
J Neurochem. 2010 Dec;115(6):1309-21. doi: 10.1111/j.1471-4159.2010.07050.x. Epub 2010 Nov 4.
Cyclin-dependent kinase (Cdk)5 is a proline-directed Ser/Thr protein kinase that functions mainly in neurons and is activated by binding to a regulatory subunit, p35 or p39. Kinase activity is mainly determined by the amount of p35 available, which is controlled by a balance between synthesis and degradation. Kinase activity is also regulated by Cdk5 phosphorylation, but the activity of phosphorylated Cdk5 is in contrast to that of cycling Cdks. Cdk5 is a versatile protein kinase that regulates multiple neuronal activities including neuronal migration and synaptic signaling. Further, Cdk5 plays a role in both survival and death of neurons. Long-term inactivation of Cdk5 triggers cell death, and the survival activity of Cdk5 is apparent when neurons suffer from stress. In contrast, hyper-activation of Cdk5 by p25 promotes cell death, probably by reactivating cell-cycle machinery in the nucleus. The pro-death activity is suppressed by membrane association of Cdk5 via myristoylation of p35. Appropriate activity, localization, and regulation of Cdk5 may be critical for long-term survival of neurons, which is more than 80 years in the case of humans.
周期蛋白依赖性激酶（Cdk）5 是一种脯氨酸导向的丝氨酸/苏氨酸蛋白激酶，主要在神经元中发挥作用，并通过与调节亚基 p35 或 p39 结合而被激活。激酶活性主要取决于可用的 p35 量，而 p35 的量是由合成和降解之间的平衡来控制的。激酶活性还受到 Cdk5 磷酸化的调节，但磷酸化 Cdk5 的活性与循环 Cdks 的活性相反。Cdk5 是一种多功能蛋白激酶，可调节多种神经元活动，包括神经元迁移和突触信号转导。此外，Cdk5 在神经元的存活和死亡中都发挥作用。长期失活 Cdk5 会引发细胞死亡，而当神经元受到应激时，Cdk5 的存活活性就会显现出来。相反，p25 过度激活 Cdk5 可能通过 p35 的豆蔻酰化促进核内细胞周期机制的重新激活，从而促进细胞死亡。通过 p35 的豆蔻酰化，Cdk5 与膜结合会抑制促死亡活性。Cdk5 的适当活性、定位和调节可能对神经元的长期存活至关重要，人类的神经元存活时间超过 80 年。
