Stress pathway activation induces phosphorylation of retinoid X receptor

Ho Young Lee, Young Ah Suh, Megan J. Robinson, John L. Clifford, Waun K. Hong, James R. Woodgett, Melanie H. Cobb, David J. Mangelsdorf, Jonathan M. Kurie

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


Cellular stresses inhibit retinoid signaling, but the molecular basis for this phenomenon has not been revealed. Here, we present evidence that retinoid X receptor (RXR) is a substrate for both mitogen-activated protein kinase kinase-4 (MKK4/SEK1) and its downstream mediator c-Jun N-terminal kinase (JNK). MKK4/SEK1 and JNK recognized distinct features on RXR in the DE and AB regions, respectively. Phosphorylation by MKK4/SEK1 had profound effects on the biochemical properties of RXR, inhibiting the expression of genes activated by RXR-retinoic acid receptor complexes. Tyr-249 in the RXR DE region was required for the inhibitory effect of MKK4/SEK1. These effects were significantly reduced in MKK4/SEK1-null cells, indicating that MKK4/SEK1 is required for the suppression of retinoid signaling by stress. Findings presented here demonstrafe that MKK4/SEK1 can directly modulate transcription by phosphorylating RXR, a novel MKK4/SEK1 substrate.

Original languageEnglish (US)
Pages (from-to)32193-32199
Number of pages7
JournalJournal of Biological Chemistry
Issue number41
StatePublished - Oct 13 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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