ArticleScientific reports2016
Exchange factors directly activated by cAMP mediate melanocortin 4 receptor-induced gene expression.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Mice lacking β-arrestin-2 in melanocortin 4 receptor-expressing neurons show marked metabolic deficits.JCI insight · 2026Article
- Primary cilia and neural computation.Journal of biomedical science · 2026Review
- Exploring Autosomal Dominant Non-Syndromic Monogenic Obesity: From Genes to Therapy.Current issues in molecular biology · 2026Review
- Development of a genetically encoded melanocortin sensor for high sensitivity in vivo imaging.Molecular metabolism · 2025Article
- Neuroendocrinology and the Genetics of Obesity.Endocrinology · 2025Review
- Decreased CREB phosphorylation impairs embryonic retinal neurogenesis in thebioRxiv : the preprint server for biology · 2024Article
- Recent Research on Mechanisms of Feeding Regulation in Chicks.The journal of poultry science · 2024Review
- Functional Characterization of NovelInternational journal of molecular sciences · 2023Article
- A unique melanocortin-4-receptor signaling profile for obesity-associated constitutively active variants.Journal of molecular endocrinology · 2023Article
- Melanocortin-4 receptor complexity in energy homeostasis,obesity and drug development strategies.Diabetes, obesity & metabolism · 2022Review
- The Role of Melanocortin Plasticity in Pain-Related Outcomes After Alcohol Exposure.Frontiers in psychiatry · 2021Review
- The melanocortin pathway and control of appetite-progress and therapeutic implications.The Journal of endocrinology · 2019Review
- Cyclic AMP-dependent protein kinase A and EPAC mediate VIP and secretin stimulation of PAK4 and activation of NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Insulin-like growth factor-1 acts as a zeitgeber on hypothalamic circadian clock gene expression via glycogen synthase kinase-3β signaling.The Journal of biological chemistry · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Functional and cardioprotective effects of simultaneous and individual activation of protein kinase A and Epac.British journal of pharmacology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gs protein-coupled receptors regulate many vital body functions by activation of cAMP response elements (CRE) via cAMP-dependent kinase A (PKA)-mediated phosphorylation of the CRE binding protein (CREB). Melanocortin 4 receptors (MC4R) are prototypical Gs-coupled receptors that orchestrate the hypothalamic control of food-intake and metabolism. Remarkably, the significance of PKA for MC4R-induced CRE-dependent transcription in hypothalamic cells has not been rigorously interrogated yet. In two hypothalamic cell lines, we observed that blocking PKA activity had only weak or no effects on reporter gene expression. In contrast, inhibitors of exchange factors directly activated by cAMP-1/2 (EPAC-1/2) mitigated MC4R-induced CRE reporter activation and mRNA induction of the CREB-dependent genes c-fos and thyrotropin-releasing hormone. Furthermore, we provide first evidence that extracellular-regulated kinases-1/2 (ERK-1/2) activated by EPACs and not PKA are the elusive CREB kinases responsible for MC4R-induced CREB/CRE activation in hypothalamic cells. Overall, these data emphasize the pivotal role of EPACs rather than PKA in hypothalamic gene expression elicited by a prototypical Gs-coupled receptor.
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Registered trials
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 Socratic graph.