ArticleAmerican journal of respiratory cell and molecular biology2014
Basal p38 mitogen-activated protein kinase regulates unliganded glucocorticoid receptor function in airway smooth muscle cells.
Article in American journal of respiratory cell and molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- How post-translational modifications impact glucocorticoid receptor function in human pathologies.Cell communication and signaling : CCS · 2026Review
- Glucocorticoids and Neutrophil Biology: Impact on the Development of Resistance to Glucocorticoid Therapy.Neuroimmunomodulation · 2026Review
- TRPM2 exacerbates airway inflammation by regulating oxidized-CaMKⅡ in allergic asthma.Heliyon · 2024Article
- Mechanism of tacrolimus in the treatment of lupus nephritis.Frontiers in pharmacology · 2024Review
- Discovery of pharmacological effects and targets ofFood & nutrition research · 2024Article
- Glucocorticoid Insensitivity in Asthma: The Unique Role for Airway Smooth Muscle Cells.International journal of molecular sciences · 2022Review
- Crosstalk between p38 MAPK and GR Signaling.International journal of molecular sciences · 2022Review
- Oxidative Stress Promotes Corticosteroid Insensitivity in Asthma and COPD.Antioxidants (Basel, Switzerland) · 2021Review
- Dexamethasone and p38 MAPK inhibition of cytokine production from human lung fibroblasts.Fundamental & clinical pharmacology · 2021Article
- P38 MAPK and glucocorticoid receptor crosstalk in bronchial epithelial cells.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Inhibition of Microglial Activation in the Amygdala Reverses Stress-Induced Abdominal Pain in the Male Rat.Cellular and molecular gastroenterology and hepatology · 2020Article
- β-Arrestin-1 inhibits glucocorticoid receptor turnover and alters glucocorticoid signaling.The Journal of biological chemistry · 2019Article
- Airway smooth muscle cells are insensitive to the anti-proliferative effects of corticosteroids: The novel role of insulin growth factor binding Protein-1 in asthma.Immunobiology · 2019Article
- Membrane-initiated nuclear trafficking of the glucocorticoid receptor in hypothalamic neurons.Steroids · 2019Article
- Hypoxia impairs adaptation of skeletal muscle protein turnover- and AMPK signaling during fasting-induced muscle atrophy.PloS one · 2018Article
- Article
- Actions of Steroids: New Neurotransmitters.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Review
- Glucocorticoid-independent modulation of GR activity: Implications for immunotherapy.Pharmacology & therapeutics · 2016Review
- Male-specific effects of lipopolysaccharide on glucocorticoid receptor nuclear translocation in the prefrontal cortex of depressive rats.Psychopharmacology · 2016Article
- Glucocorticoid and TNF signaling converge at A20 (TNFAIP3) to repress airway smooth muscle cytokine expression.American journal of physiology. Lung cellular and molecular physiology · 2016Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Like many steroid receptors, the glucocorticoid (GC) receptor (GR) is a phosphoprotein. Although there are multiple phosphorylation sites critical for GR transcriptional activity (i.e., serine [S]203, S211, and S226), their respective role in driving GR functions is highly cell specific. We have recently identified protein phosphatase 5 as an essential Ser/Thr phosphatase responsible for impairing GR function via S211 dephosphorylation in airway smooth muscle (ASM) cells. Because p38 mitogen-activated protein kinase (MAPK) directly phosphorylates GR in different cell types in a stimulus- and cell-dependent manner, we investigated the role of p38 MAPK on GR phosphorylation and function in ASM cells. Cells were transfected with 100 nM p38 MAPK small interfering RNA or 2 μg MAPK kinase 3 expression vector (a specific kinase that directly activates p38 MAPK) in the presence or absence of fluticasone (100 nM) and/or p38 MAPK pharmacological inhibitor SB203580. We found that p38 MAPK blockade positively regulates GR nuclear translocation and GR-dependent induction of the steroid-target gene GC-induced leucine zipper in a hormone-independent manner. We also found that p38 MAPK-dependent regulation of GR functions was associated with a differential action on GR phosphorylation at S203 and S211 residues. This study demonstrated that the inactive state of GR in resting conditions is not only ensured by the absence of the GC ligand but also by p38 MAPK-dependent phosphorylation of unliganded GR at specific residues, which appears to be important in determining the overall GC responsiveness of ASM cells.
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