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

Andrew D. Wingate, David G. Campbell, Mark Peggie, J. Simon C. Arthur

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)

Abstract

Nur77 is a nuclear orphan receptor that is able to activate transcription independently of exogenous ligand, and has also been shown to promote apoptosis on its localization to mitochondria. Phosphorylation of Nur77 on Ser 354 has been suggested to reduce ability of Nur77 to bind DNA; however, the kinase responsible for this phosphorylation in cells has not been clearly established. In the present study, we show that Nur77 is phosphorylated on this site by RSK (ribosomal S6 kinase) and MSK (mitogen- and stress-activated kinase), but not by PKB (protein kinase B) or PKA (protein kinase A), in vitro. In cells, phosphorylation of Nur77 in vivo is catalysed by RSK, which is activated downstream of the classical MAPK (mitogen-activated protein kinase) cascade. Phosphorylation of Nur77 by RSK is able to promote the binding of Nur77 to 14-3-3 proteins in vitro, however, no evidence could be seen for this interaction in cells. We have established that two related proteins, Nurr1 and Nor1, are also phosphorylated on the equivalent site by RSK in cells in response to mitogenic stimulation.

Original languageEnglish
Pages (from-to)715-724
Number of pages10
JournalBiochemical Journal
Volume393
Issue number3
Early online date13 Jan 2006
DOIs
Publication statusPublished - 1 Feb 2006

Keywords

  • Apoptosis
  • Nuclear orphan receptor
  • Nur77
  • Phosphorylation
  • Protein kinase B (PKB)
  • Ribosomal S6 kinase (RSK)

Fingerprint

Dive into the research topics of 'Nur77 is phosphorylated in cells by RSK in response to mitogenic stimulation'. Together they form a unique fingerprint.

Cite this