C-Jun N-terminal kinase 2 phosphorylates endothelial nitric oxide synthase at serine 116 and regulates nitric oxide production

Jung Hyun Park, Meanha Park, Catherine Jeonghae Byun, Inho Jo

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


The c-Jun N-terminal kinases (JNKs) belonging to the mitogen-activated protein kinase (MAPK) superfamily play important roles in foam-cell formation, hypercholesterolemia-mediated endothelial dysfunction, and the development of obesity. Although decreased nitric oxide (NO) production via decreased phosphorylation of endothelial NO synthase at serine 1179 (eNOS-Ser 1179) was reported to be partly involved in JNK2-derived endothelial dysfunction, JNK2 seems likely to be indirectly involved in this signaling pathway. Here, using bovine aortic endothelial cells, we examined whether JNK2 directly phosphorylated eNOS-Ser 116, a putative substrate site for the MAPK superfamily, and this phosphorylation resulted in decreased NO release. JNK inhibitor SP60012 increased NO release in a time- and dose-dependent manner, which was accompanied by increased eNOS-Ser 116 phosphorylation. Purified JNK2 directly phosphorylated eNOS-Ser 116 in vitro. Ectopic expression of dominant negative JNK2 repressed eNOS-Ser 116 phosphorylation and increased NO production. Coimmunoprecipitation and confocal microscopy studies revealed a colocalization of eNOS and JNK2. However, all these observed effects were not manifested when JNK1 probes were used. Overall, this study indicates that JNK2 is a physiological kinase responsible for eNOS-Ser 116 phosphorylation and regulates NO production.

Original languageEnglish
Pages (from-to)340-345
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - 6 Jan 2012

Bibliographical note

Funding Information:
This work was supported by the RP-Grant 2009 of Ewha Womans University.


  • C-Jun N-terminal kinase 2
  • Endothelial nitric oxide synthase
  • Nitric oxide
  • Phosphorylation
  • Signal transduction


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