Cdk5/p35 phosphorylates lemur tyrosine kinase-2 to regulate protein phosphatase-1C phosphorylation and activity
Cdk5/p35 phosphorylates lemur tyrosine kinase-2 to regulate protein phosphatase-1C phosphorylation and activity
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DOI：
10.1111/j.1471-4159.2012.07650.x
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发表时间：
2012-05-01
影响因子：
4.7
通讯作者：
Miller, Christopher C. J.
中科院分区：
文献类型：
--
作者：
Manser, Catherine;Vagnoni, Alessio;Miller, Christopher C. J.
细胞周期蛋白依赖性激酶-5(CDK5/p35)和蛋白磷酸酶-1(PP1)是控制神经系统内多种生理过程的两种主要酶，包括神经元分化、突触可塑性和轴突运输。CDK5/p35和PP1功能缺陷也与人类几种主要的神经退行性疾病有关。CDK5/p35和PP1的催化亚单位(PP1C)都与大脑丰富的丝氨酸激酶狐猴酪氨酸激酶-2(LMTK2)结合。此外，LMTK2使苏氨酸-320(PP1Chor320)上的PP1C磷酸化，从而抑制其活性。在这里，我们证明了LMTK2被CDK5/p35磷酸化在丝氨酸-1418(LMTK2ser1418)上，并提供了证据表明这调节了它磷酸化PP1Cth320的能力。因此，我们描述了神经系统内连接CDK5/p35和PP1C的新的信号通路，该通路与许多神经元功能和神经元功能障碍有关。
Cyclin-dependent kinase-5 (cdk5)/p35 and protein phosphatase-1 (PP1) are two major enzymes that control a variety of physiological processes within the nervous system including neuronal differentiation, synaptic plasticity and axonal transport. Defective cdk5/p35 and PP1 function are also implicated in several major human neurodegenerative diseases. Cdk5/p35 and the catalytic subunit of PP1 (PP1C) both bind to the brain-enriched, serinethreonine kinase lemur tyrosine kinase-2 (LMTK2). Moreover, LMTK2 phosphorylates PP1C on threonine-320 (PP1Cthr320) to inhibit its activity. Here, we demonstrate that LMTK2 is phosphorylated on serine-1418 (LMTK2ser1418) by cdk5/p35 and present evidence that this regulates its ability to phosphorylate PP1Cthr320. We thus describe a new signalling pathway within the nervous system that links cdk5/p35 with PP1C and which has implications for a number of neuronal functions and neuronal dysfunction.