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

Jung-Hyun Park1, Meanha Park, Catherine Jeonghae Byun

  • 1Department of Molecular Medicine and Ewha Medical Research Institute, Ewha Womans University Medical School, Seoul, South Korea.

Biochemical and Biophysical Research Communications
|December 14, 2011
PubMed

Insights

c-Jun N-terminal kinase 2 (JNK2) directly phosphorylates endothelial nitric oxide synthase (eNOS) at serine 116, reducing nitric oxide (NO) production. This finding clarifies JNK2

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Cardiovascular Research

Background:

  • Mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinases (JNKs), are implicated in endothelial dysfunction.
  • Previous studies suggested JNK2's indirect role in endothelial dysfunction via reduced nitric oxide (NO) production.
  • The specific mechanism of JNK2 action on endothelial NO synthase (eNOS) remained unclear.

Purpose of the Study:

  • To investigate whether JNK2 directly phosphorylates eNOS at serine 116 (eNOS-Ser116).
  • To determine if JNK2-mediated eNOS-Ser116 phosphorylation decreases NO release.
  • To elucidate the direct role of JNK2 in regulating NO production in endothelial cells.

Main Methods:

  • Utilized bovine aortic endothelial cells.
  • Employed JNK inhibitor SP60012 to assess effects on NO release and eNOS-Ser116 phosphorylation.
  • Performed in vitro kinase assays with purified JNK2.
  • Used dominant-negative JNK2 expression, coimmunoprecipitation, and confocal microscopy.

Main Results:

  • JNK inhibition increased NO release and eNOS-Ser116 phosphorylation.
  • Purified JNK2 directly phosphorylated eNOS-Ser116 in vitro.
  • Dominant-negative JNK2 reduced eNOS-Ser116 phosphorylation and enhanced NO production.
  • eNOS and JNK2 were found to colocalize.
  • JNK1 did not produce similar effects, indicating specificity for JNK2.

Conclusions:

  • JNK2 directly phosphorylates eNOS at Serine 116.
  • This phosphorylation event by JNK2 leads to decreased nitric oxide production.
  • JNK2 is identified as a physiological kinase regulating eNOS activity and NO release.

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