Antagonism of glucocorticoid receptor transcriptional activation by the c-Jun N-terminal kinase
- 3 March 1998
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 95 (5) , 2050-2055
- https://doi.org/10.1073/pnas.95.5.2050
Abstract
The mitogen-activated protein kinases ERK (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase), and p38 phosphorylate and activate transcription factors that promote proliferative and inflammatory responses, whereas glucocorticoid receptor (GR) activation inhibits cell growth and inflammation. We demonstrate that JNK and ERK but not p38 phosphorylate GR in vitro primarily at Ser-246. Selective activation of either ERK or JNK in vivo inhibits GR-mediated transcriptional activation, which depends on receptor phosphorylation at Ser-246 by JNK but not ERK. Thus, JNK inhibits GR transcriptional activation by direct receptor phosphorylation, whereas ERK does so indirectly. We propose that phosphorylation of GR by JNK or of a GR cofactor by ERK provides mechanisms to ensure the rapid inhibition of GR-dependent gene expression when it conflicts with mitogenic or proinflammatory signals.Keywords
This publication has 36 references indexed in Scilit:
- Stress-Induced Phosphorylation and Activation of the Transcription Factor CHOP (GADD153) by p38 MAP KinaseScience, 1996
- Molecular mechanisms of anti‐inflammatory action of glucocorticoidsBioEssays, 1996
- Selective activation of the JNK signaling cascadeand c-Jun transcriptional activity by the small GTPases Rac and Cdc42HsCell, 1995
- Pro-inflammatory Cytokines and Environmental Stress Cause p38 Mitogen-activated Protein Kinase Activation by Dual Phosphorylation on Tyrosine and ThreonineJournal of Biological Chemistry, 1995
- Membrane targeting of the nucleotide exchange factor Sos is sufficient for activating the Ras signaling pathwayCell, 1994
- A MAP Kinase Targeted by Endotoxin and Hyperosmolarity in Mammalian CellsScience, 1994
- JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domainPublished by Elsevier ,1994
- Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain.Genes & Development, 1993
- The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1Nature, 1993
- STEROID RECEPTOR REGULATED TRANSCRIPTION OF SPECIFIC GENES AND GENE NETWORKSAnnual Review of Genetics, 1985