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Nur77 is phosphorylated in cells by RSK in response to mitogenic stimulation

Andrew D Wingate1, David G Campbell, Mark Peggie

  • 1MRC Protein Phosphorylation Unit, Faculty of Life Sciences, University of Dundee, Dundee, Scotland DD1 5EH, UK.

The Biochemical Journal
|October 15, 2005
PubMed

Insights

Ribosomal S6 kinase (RSK) phosphorylates the nuclear orphan receptor Nur77 at Ser354, impacting its DNA binding. This RSK-mediated phosphorylation is crucial for Nur77 regulation in response to mitogenic signals.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Nur77 is a nuclear orphan receptor involved in transcription and apoptosis.
  • Phosphorylation at Ser354 may inhibit Nur77's DNA binding, but the responsible kinase is unknown.

Purpose of the Study:

  • Identify the kinase responsible for Nur77 phosphorylation at Ser354 in cells.
  • Investigate the functional consequences of this phosphorylation.

Main Methods:

  • In vitro kinase assays using purified kinases and Nur77.
  • In vivo studies in cell cultures to assess phosphorylation and protein interactions.
  • Analysis of related proteins Nurr1 and Nor1 phosphorylation.

Main Results:

  • RSK and MSK (mitogen- and stress-activated kinase) phosphorylate Nur77 at Ser354 in vitro.
  • RSK, activated by the MAPK cascade, is the primary kinase for Nur77 phosphorylation in cells.
  • Nur77 phosphorylation by RSK promotes 14-3-3 binding in vitro, but not in cells.
  • RSK also phosphorylates related proteins Nurr1 and Nor1.

Conclusions:

  • RSK is the key kinase phosphorylating Nur77 at Ser354 in response to mitogenic stimuli.
  • This phosphorylation event is conserved in related NR4A family members.
  • Further research is needed to clarify the in vivo implications of RSK-mediated Nur77 phosphorylation.

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