| Literature DB >> 20980593 |
Peng Zhang1, Pei-Chun Yu, Anthony H K Tsang, Yu Chen, Amy K Y Fu, Wing-Yu Fu, Kenny K Chung, Nancy Y Ip.
Abstract
Precise regulation of cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase family, is critical for proper neuronal development and functions. Cdk5 is activated through its association with the neuron-specific activator p35 or p39. Nonetheless, how its kinase activity is regulated in neurons is not well understood. In this study, we found that Cdk5 activity is regulated by S-nitrosylation, a post-translational modification of protein that affects a plethora of neuronal functions. S-nitrosylation of Cdk5 occurs at Cys83, which is one of the critical amino acids within the ATP-binding pocket of the kinase. Upon S-nitrosylation, Cdk5 exhibits reduced kinase activity, whereas mutation of Cys83 to Ala on Cdk5 renders the kinase refractory to such inhibition. Importantly, S-nitrosylated Cdk5 can be detected in the mouse brain, and blocking the S-nitrosylation of Cdk5 in cultured hippocampal neurons enhances dendritic growth and branching. Together, our findings reveal an important role of S-nitrosylation in regulating Cdk5 kinase activity and dendrite growth in neurons during development.Entities:
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Year: 2010 PMID: 20980593 PMCID: PMC6634798 DOI: 10.1523/JNEUROSCI.3899-10.2010
Source DB: PubMed Journal: J Neurosci ISSN: 0270-6474 Impact factor: 6.167