Xie Zhigang, Tsai Li-Huei
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell Cycle. 2004 Feb;3(2):108-10.
Cdk5 is a member of the cyclin-dependent kinase (Cdk) family. Unlike other Cdks that promote cell cycle, Cdk5 is activated in postmitotic neurons and critically regulates neuronal migration by phosphorylating its substrates during brain development. Recently, we found that Cdk5 phosphorylates focal adhesion kinase (FAK) at Serine 732 in vitro and is responsible for this phosphorylation in the developing brain. Our experiments using a phospho-specific antibody and an S732-unphosphorylatable mutant FAK suggest that S732 phosphorylation may regulate a centrosome-associated microtubule structure to promote nuclear translocation, a critical step in neuronal migration. S732 phosphorylation does not directly impact on the kinase activity of FAK, but appears to prevent the accumulation of FAK at the centrosome. Our study reveals a similarity between Cdk5 and Cdk1 in the regulation of neuronal migration and cell division, respectively. In addition, our study implicates FAK in a signaling pathway that directly regulates microtubules.
Cdk5是细胞周期蛋白依赖性激酶（Cdk）家族的成员。与其他促进细胞周期的Cdk不同，Cdk5在有丝分裂后的神经元中被激活，并在大脑发育过程中通过磷酸化其底物来严格调控神经元迁移。最近，我们发现Cdk5在体外可在丝氨酸732位点磷酸化粘着斑激酶（FAK），并且在发育中的大脑中负责这种磷酸化。我们使用磷酸特异性抗体和S732不可磷酸化的突变型FAK进行的实验表明，S732磷酸化可能调节与中心体相关的微管结构以促进核转位，这是神经元迁移中的关键步骤。S732磷酸化不会直接影响FAK的激酶活性，但似乎可防止FAK在中心体处积累。我们的研究揭示了Cdk5和Cdk1分别在神经元迁移和细胞分裂调控方面的相似性。此外，我们的研究表明FAK参与了直接调节微管的信号通路。
