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 journalArticle

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Abstract

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
Volume275
Issue number41
StatePublished - Oct 13 2000

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Retinoid X Receptors
Phosphorylation
Chemical activation
Retinoids
MAP Kinase Kinase 4
Null Lymphocytes
Retinoic Acid Receptors
JNK Mitogen-Activated Protein Kinases
Substrates
Transcription
Phosphotransferases
Genes
Gene Expression

ASJC Scopus subject areas

  • Biochemistry

Cite this

Lee, H. Y., Suh, Y. A., Robinson, M. J., Clifford, J. L., Hong, W. K., Woodgett, J. R., ... Kurie, J. M. (2000). Stress pathway activation induces phosphorylation of retinoid X receptor. Journal of Biological Chemistry, 275(41), 32193-32199.

Stress pathway activation induces phosphorylation of retinoid X receptor. / Lee, Ho Young; Suh, Young Ah; Robinson, Megan J.; Clifford, John L.; Hong, Waun K.; Woodgett, James R.; Cobb, Melanie H.; Mangelsdorf, David J.; Kurie, Jonathan M.

In: Journal of Biological Chemistry, Vol. 275, No. 41, 13.10.2000, p. 32193-32199.

Research output: Contribution to journalArticle

Lee, HY, Suh, YA, Robinson, MJ, Clifford, JL, Hong, WK, Woodgett, JR, Cobb, MH, Mangelsdorf, DJ & Kurie, JM 2000, 'Stress pathway activation induces phosphorylation of retinoid X receptor', Journal of Biological Chemistry, vol. 275, no. 41, pp. 32193-32199.
Lee HY, Suh YA, Robinson MJ, Clifford JL, Hong WK, Woodgett JR et al. Stress pathway activation induces phosphorylation of retinoid X receptor. Journal of Biological Chemistry. 2000 Oct 13;275(41):32193-32199.
Lee, Ho Young ; Suh, Young Ah ; Robinson, Megan J. ; Clifford, John L. ; Hong, Waun K. ; Woodgett, James R. ; Cobb, Melanie H. ; Mangelsdorf, David J. ; Kurie, Jonathan M. / Stress pathway activation induces phosphorylation of retinoid X receptor. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 41. pp. 32193-32199.
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