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Updated: Jul 19, 2026

Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
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Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells

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p90 RSK-1 associates with and inhibits neuronal nitric oxide synthase

Tao Song1, Katsuyoshi Sugimoto, Hideshi Ihara

  • 1Department of Cell Physiology, Kagawa University, Faculty of Medicine, Kagawa 761-0793, Japan.

The Biochemical Journal
|September 21, 2006
PubMed

Insights

Ribosomal S6 kinase 1 (RSK1) directly phosphorylates neuronal nitric oxide synthase (nNOS) at Ser847, regulating nitric oxide function. This RSK1-nNOS interaction is triggered by mitogens like EGF.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Neuroscience

Background:

  • Neuronal nitric oxide synthase (nNOS) plays critical roles in the brain.
  • Mitogen-activated protein kinase (MAPK) pathways regulate cellular processes.
  • RSK1 is a key downstream kinase in the MAPK pathway.

Purpose of the Study:

  • To investigate the direct interaction and regulatory mechanism between RSK1 and nNOS.
  • To elucidate the role of RSK1 phosphorylation of nNOS in response to mitogenic stimuli.
  • To understand the functional consequences of nNOS phosphorylation on its activity.

Main Methods:

  • Cell culture (GH3, HEK-293 cells) and primary neuronal cultures (rat hippocampal, cerebellar granule cells).
  • Western blotting to detect protein phosphorylation and interaction.
  • Enzyme activity assays for nNOS.
  • Use of specific inhibitors (PD98059, Ro31-8220) and mutant nNOS (S847A).

Main Results:

  • RSK1 directly phosphorylates nNOS on Ser847 in response to epidermal growth factor (EGF).
  • EGF treatment increases nNOS Ser847 phosphorylation, inhibits NOS activity, and promotes RSK1-nNOS complex formation.
  • Inhibition of RSK1 or MEK (MAPK/extracellular-signal-regulated kinase kinase) blocks these effects.
  • Mutant nNOS (S847A) is resistant to phosphorylation and activity changes.
  • nNOS phosphorylation at Ser847 by RSK1 occurs in neuronal cells.

Conclusions:

  • RSK1 is a direct regulator of nNOS activity through phosphorylation at Ser847.
  • This signaling pathway is activated by mitogens and plays a role in regulating nitric oxide function in the brain.
  • The findings reveal a novel mechanism for controlling nNOS activity in neurons.

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