CDK5 phosphorylates eNOS at Ser-113 and regulates NO production

Chien Hsing Lee, Yin Win Wei, Yi Ting Huang, Yuh Te Lin, Yu Cheng Lee, Kuen Haur Lee, Pei Jung Lu

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Phosphorylation of endothelial nitric oxide synthase (eNOS) is key mechanism in response to various forms of cellular stimulation. Through protein nitration by peroxynitrite, eNOS is believed to be responsible for the major abnormalities in several important neurodegenerative diseases including Alzheimer's (AD) and Parkinson's diseases (PD). Recent studies provide important in vivo evidence that hyperactivation of Cdk5 by p25 plays an essential role in the cell death of neurons in experimental models of AD and PD. This study focuses on the functional regulation of eNOS by Cdk5/p35 complex in a phosphorylation dependent manner. Our results showed that Cdk5 can phosphorylate eNOS both in vitro and in vivo. In vitro kinase assay together with the bioinformatic analysis and site direct mutagenesis revealed that Ser-113 is the major phosphorylation site for Cdk5. Most interestingly, the nitrite production was significantly reduced in eNOS and Cdk5/p35 cotransfected SH-SY5Y cells when compared with co-transfection of Cdk5/p35 and S113A. Together, our data suggest that Cdk5 can phosphorylate eNOS at the Ser-113 site and down-regulate eNOS-derived NO levels.

Original languageEnglish
Pages (from-to)112-117
Number of pages6
JournalJournal of Cellular Biochemistry
Volume110
Issue number1
DOIs
Publication statusPublished - May 1 2010
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type III
Phosphorylation
Parkinson Disease
Neurodegenerative diseases
Nitration
Mutagenesis
Peroxynitrous Acid
Cell death
Bioinformatics
Nitrites
Computational Biology
Neurodegenerative Diseases
Neurons
Transfection
Assays
Alzheimer Disease
Cell Death
Theoretical Models
Phosphotransferases
Down-Regulation

Keywords

  • Alzheimer's diseases
  • Cdk5
  • eNOS
  • NO
  • Parkinson's diseases

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Lee, C. H., Wei, Y. W., Huang, Y. T., Lin, Y. T., Lee, Y. C., Lee, K. H., & Lu, P. J. (2010). CDK5 phosphorylates eNOS at Ser-113 and regulates NO production. Journal of Cellular Biochemistry, 110(1), 112-117. https://doi.org/10.1002/jcb.22515

CDK5 phosphorylates eNOS at Ser-113 and regulates NO production. / Lee, Chien Hsing; Wei, Yin Win; Huang, Yi Ting; Lin, Yuh Te; Lee, Yu Cheng; Lee, Kuen Haur; Lu, Pei Jung.

In: Journal of Cellular Biochemistry, Vol. 110, No. 1, 01.05.2010, p. 112-117.

Research output: Contribution to journalArticle

Lee, CH, Wei, YW, Huang, YT, Lin, YT, Lee, YC, Lee, KH & Lu, PJ 2010, 'CDK5 phosphorylates eNOS at Ser-113 and regulates NO production', Journal of Cellular Biochemistry, vol. 110, no. 1, pp. 112-117. https://doi.org/10.1002/jcb.22515
Lee, Chien Hsing ; Wei, Yin Win ; Huang, Yi Ting ; Lin, Yuh Te ; Lee, Yu Cheng ; Lee, Kuen Haur ; Lu, Pei Jung. / CDK5 phosphorylates eNOS at Ser-113 and regulates NO production. In: Journal of Cellular Biochemistry. 2010 ; Vol. 110, No. 1. pp. 112-117.
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