ArticleMolecular endocrinology (Baltimore, Md.)2011
Signaling from the human melanocortin 1 receptor to ERK1 and ERK2 mitogen-activated protein kinases involves transactivation of cKIT.
Article in Molecular endocrinology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 97 citations in OpenAlex.
- The anti-inflammatory efficacy of melanocortin drugs is influenced by genetic variation at MC1R.Scientific reports · 2026Article
- Article
- Vitiligo as a Failure of Immune Resolution and Tissue Regeneration: From Stress Signals to Targeted Immune Modulation.Clinical reviews in allergy & immunology · 2026Review
- Dissecting the boundary of quiescence and activation of murine melanocyte stem cells in the hair follicle niche.NPJ Regenerative medicine · 2026Review
- Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases.Diseases (Basel, Switzerland) · 2025Review
- Advances in Pathogenesis and Treatment of Skin Cancer.International journal of molecular sciences · 2025Article
- An overview of benefits and risks of chronic melanocortin-1 receptor activation.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025Review
- Journey through the spectacular landscape of melanocortin 1 receptor.Pigment cell & melanoma research · 2024Review
- Review
- Anti-Melanogenic Effects ofPlants (Basel, Switzerland) · 2023Article
- MC1R signaling through the cAMP-CREB/ATF-1 and ERK-NFκB pathways accelerates G1/S transition promoting breast cancer progression.NPJ precision oncology · 2023Article
- Alpha-melanocyte stimulating hormone (α-MSH): biology, clinical relevance and implication in melanoma.Journal of translational medicine · 2023Review
- Melanocortin 1 Receptor (MC1R): Pharmacological and Therapeutic Aspects.International journal of molecular sciences · 2023Review
- The journey from melanocytes to melanoma.Nature reviews. Cancer · 2023Review
- MGRN1 as a Phenotypic Determinant of Human Melanoma Cells and a Potential Biomarker.Life (Basel, Switzerland) · 2022Article
- Dimethyl Itaconate Reduces α-MSH-Induced Pigmentation via Modulation of AKT and p38 MAPK Signaling Pathways in B16F10 Mouse Melanoma Cells.Molecules (Basel, Switzerland) · 2022Article
- Revealing the genetic basis of eyelid pigmentation in Hereford cattle.Journal of animal science · 2022Article
- The Dark Side of Melanin Secretion in Cutaneous Melanoma Aggressiveness.Frontiers in oncology · 2022Review
- [Neuroimmunomodulation in allergic rhinitis].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2021Article
- Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Melanocortin 1 receptor (MC1R), a Gs protein-coupled receptor expressed in melanocytes, is a major determinant of skin pigmentation, phototype and cancer risk. Upon stimulation by αMSH, MC1R triggers the cAMP and ERK1/ERK2 MAPK pathways. In mouse melanocytes, ERK activation by αMSH binding to Mc1r depends on cAMP, and melanocytes are considered a paradigm for cAMP-dependent ERK activation. However, human MC1R variants associated with red hair, fair skin [red hair color (RHC) phenotype], and increased skin cancer risk display reduced cAMP signaling but activate ERKs as efficiently as wild type in heterologous cells, suggesting independent signaling to ERKs and cAMP in human melanocytes. We show that MC1R signaling activated the ERK pathway in normal human melanocytes and melanoma cells expressing physiological levels of endogenous RHC variants. ERK activation was comparable for wild-type and mutant MC1R and was independent on cAMP because it was neither triggered by stimulation of cAMP synthesis with forskolin nor blocked by the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine. Stimulation of MC1R with αMSH did not lead to protein kinase C activation and ERK activation was unaffected by protein kinase C inhibitors. Conversely, pharmacological interference, small interfering RNA studies, expression profiles, and functional reconstitution experiments showed that αMSH-induced ERK activation resulted from Src tyrosine kinase-mediated transactivation of the stem cell factor receptor, a receptor tyrosine kinase essential for proliferation, differentiation, and survival of melanocyte precursors, thus demonstrating a functional link between the stem cell factor receptor and MC1R. Moreover, this transactivation phenomenon is unique because it is unaffected by natural mutations impairing canonical MC1R signaling through the cAMP pathway.
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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.