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- Title
S-Nitrosylation of Cyclin-Dependent Kinase 5 (Cdk5) Regulates Its Kinase Activity and Dendrite Growth During Neuronal Development.
- Authors
Peng Zhang; Pei-Chun Yu; Tsang, Anthony H. K.; 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 AlP-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 CdkS 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.
- Subjects
CYCLIN-dependent kinases; DENDRITES; AMINO acids; BRAIN research; TYROSINE
- Publication
Journal of Neuroscience, 2010, Vol 30, Issue 43, p14366
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3899-10.2010