ArticleMolecular endocrinology (Baltimore, Md.)2009
cAMP enhances estrogen-related receptor alpha (ERRalpha) transcriptional activity at the SP-A promoter by increasing its interaction with protein kinase A and steroid receptor coactivator 2 (SRC-2).
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- An ERRα-ZEB1 transcriptional signature predicts survival in triple-negative breast cancers.Molecular medicine (Cambridge, Mass.) · 2026Article
- Hepatocyte estrogen-related receptor α modulates a gluconeogenic-epigenetic crosstalk counteracting MASLD/MASH progression.Experimental & molecular medicine · 2026Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Evaluation of Protein Kinase cAMP-Activated Catalytic Subunit Alpha as a Therapeutic Target for Fibrolamellar Carcinoma.Gastro hep advances · 2023Article
- Role of NRF2 in immune modulator expression in developing lung.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Inhibition of Estrogen-Related Receptor α Blocks Liver Steatosis and Steatohepatitis and Attenuates Triglyceride Biosynthesis.The American journal of pathology · 2021Article
- ERRγ enhances cardiac maturation with T-tubule formation in human iPSC-derived cardiomyocytes.Nature communications · 2021Article
- Differential Regulation of Human Surfactant Protein A Genes, SFTPA1 and SFTPA2, and Their Corresponding Variants.Frontiers in immunology · 2021Review
- Decreased 11β-hydroxysteroid dehydrogenase 1 in lungs of steroid receptor coactivator (Src)-1/-2 double-deficient fetal mice is caused by impaired glucocorticoid and cytokine signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Regulation of the expression of the estrogen related receptors (ERRs).Cellular and molecular life sciences : CMLS · 2020Review
- PGC1α Inhibits Polyamine Synthesis to Suppress Prostate Cancer Aggressiveness.Cancer research · 2019Article
- Multifactorial Regulation of Myometrial Contractility During Pregnancy and Parturition.Frontiers in endocrinology · 2019Review
- ERRα as a Bridge Between Transcription and Function: Role in Liver Metabolism and Disease.Frontiers in endocrinology · 2019Review
- Developmental Decline in the MicroRNA 199a (miR-199a)/miR-214 Cluster in Human Fetal Lung Promotes Type II Cell Differentiation by Upregulating Key Transcription Factors.Molecular and cellular biology · 2018Article
- Fetal-to-maternal signaling in the timing of birth.The Journal of steroid biochemistry and molecular biology · 2017Review
- Steroid receptor coactivators as therapeutic targets in the female reproductive system.The Journal of steroid biochemistry and molecular biology · 2015Review
- Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition.The Journal of clinical investigation · 2015Article
- Fetal-to-maternal signaling to initiate parturition.The Journal of clinical investigation · 2015Article
- Estrogen-Related Receptors in Breast Cancer and Prostate Cancer.Frontiers in endocrinology · 2015Review
- Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Estrogen-related receptor (ERRalpha) plays a critical role in basal and cAMP-induced expression of the human surfactant protein-A (SP-A) gene in lung type II cells through direct binding to an ERR response element (ERRE, 5'-TGACCTTA-3') within its 5'-flanking region. Furthermore, protein kinase A (PKA) up-regulates ERRalpha activation of the hSP-A promoter. In the present study, using cultured human fetal lung type II cells, we observed that cAMP enhanced ERRalpha phosphorylation and nuclear expression levels. cAMP/PKA stimulation of ERRalpha activation of the SP-A promoter was blocked by the PKA inhibitor, H89, whereas the MAPK P38 inhibitor, SB203580, and the MAPK kinase inhibitor, PD98059, had negligible to modest effects. This suggests that cAMP acts selectively through PKA to increase ERRalpha transcriptional activity. Of several coactivators tested, steroid receptor coactivator 2 (SRC-2) had the most pronounced effect to increase ERRalpha transcriptional activity at the SP-A promoter; this was enhanced by cotransfection with PKA catalytic subunit (PKAcat). Interestingly, SRC-2, ERRalpha, and PKAcat in type II cell nuclear extracts interacted at the ERRE; this was enhanced by cAMP and inhibited by H89. cAMP increased in vivo binding of PKAcat and SRC-2 to the ERRE genomic region in lung type II cells. In mutagenesis studies, three serines (S87, S114, and S277) were found to be critical for PKA and SRC-2 induction of ERRalpha transcriptional activity. Collectively, these findings indicate that cAMP/PKA signaling enhances ERRalpha phosphorylation and nuclear localization, recruitment to the SP-A promoter, and interaction with PKAcat and SRC-2, resulting in the up-regulation of SP-A gene transcription.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.