Activation or inactivation mechanism of brain cdc2-like kinase, cdk5

周期性依赖因子是eukaryotic cells中细胞周期的进展中的关键因素。CDK 5是一种独特的CDK全体激酶活动，仅在后代谢神经元中检测到。关于CDK 5在神经迁移或定位过程中通过磷酸化的轴细胞keletons（如微管相关蛋白tau和神经膜）中的几条证据线建议。不管怎样，我们还不知道它的激酶活动是如何调节的。我们在这里研究CDK5.1的激活或不激活机制。我们研究了CDK 5中的激活机制，使用主文化神经元作为一个标记。CDK 5在4至5天后被激活，当神经纤维素-H亚单位的磷酸化表格出现并同步形成时。添加BDNF到培养中诱导激活CDK 5。这些结果建议CDK 5的激活是由合成形式后的BDNF的秘密引起的。CDK 5是由绑定激活的子单元p35谁在神经元独占中表达出来的。P35是一种短暂的生命蛋白质在几个小时内退化。CDK 5通过降低其活动，第35页。P35被蛋白质降解，如生长细胞中的环素。磷酸化被认为是一个退化的信号。p35被蛋白质溶解到p25在从bovine或porcine brains中纯化CDK 5。蛋白质在这一有限的蛋白质中被卷入其中，它被认为是钙蛋白。Addition of CaイイD12+イエD1 to porcine brain extract induced proteolysis of p35 to p25。这种蛋白质被Calpain抑制剂抑制了。蛋白质溶解改变了CDK 5的溶解度。P35/CDK5 precipitated by Brief centrifugation became to be soluble after proteolytic conversion to p25。第35至第25页的有限蛋白质溶解在神经元细胞死亡的时候得到了增强。

Cyclin-dependent kinases are key factors in progression of cell cycle in eukaryotic cells. CDK5 is an unique CDK whosc kinase activity is detected only in post-mitotic neurons. Several lines of evidence suggest that CDK5 involves in neuronal migration or positioning during development via phosphorylation of axonal cytoskeletons such as microtubule-associated protein tau and neurofilaments. However, it is not known how its kinase activity is regulated. We investigated here the activation or inactivation mechanism of CDK5.1. We studied the activation mechanism of CDK5 in primary cultured neurons using the phosphorylation of neurofilament-H subunit as a marker. CDK5 was activated at 4 to 5 days after plating when phosphorylated form of neurofilament-H subunit appeared and synapse formation occurred. Addition of BDNF into culture medium induced activation of CDK5. These results suggest that activation of CDK5 was induced by increased secretion of BDNF after synapse formation.2. CDK5 is activated by binding to activating subunit p35 which is expressed in neurons exclusively. p35 is a short life protein degraded in a few hours. CDK5 decreased its activity along with degradation of p35. p35 was degraded by proteasome as well as cyclins in proliferating cells. Phosphorylation was suggested to be a signal for degradation.3. p35 is proteolysed to p25 during purification of CDK5 from bovine or porcine brains. Proteases involving in this limited proteolysis was shown to be calpain. Addition of CaィイD12+ィエD1 to porcine brain extract induced proteolysis of p35 to p25. This proteolysis was suppressed by calpain inhibitor. The proteolysis changed the solubility of CDK5. P35/CDK5 precipitated by brief centrifugation became to be soluble after proteolytic conversion to p25. Limited proteolysis of p35 to p25 was enhanced at the time of neuronal cell death.