ArticleNature structural & molecular biology2011
ERK and PDE4 cooperate to induce RAF isoform switching in melanoma.
Article in Nature structural & molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 89 citations in OpenAlex.
- Scalable clinical proteomics from DNA/RNA extraction flowthroughs enables integrated proteogenomic profiling from a single cancer biopsy.Clinical proteomics · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Proteogenomic characterization unveils biomarkers associated with chemoresistance in muscle-invasive bladder cancer.Cell reports. Medicine · 2025Article
- Mitochondrial signatures shape phenotype switching and apoptosis in response to PLK1 inhibitors.Life science alliance · 2025Article
- The multifaceted role of phosphodiesterase 4 in tumor: from tumorigenesis to immunotherapy.Frontiers in immunology · 2025Review
- PDE4D drives rewiring of the MAPK pathway in BRAF-mutated melanoma resistant to MAPK inhibitors.Cell communication and signaling : CCS · 2024Article
- A bioluminescent and homogeneous assay for monitoring GPCR-mediated cAMP modulation and PDE activity.Scientific reports · 2024Article
- PDE4B promotes the progression of gastric cancer via the PI3K/AKT/MYC pathway and immune infiltration.American journal of cancer research · 2024Article
- Development of a Macrophage-Related Risk Model for Metastatic Melanoma.International journal of molecular sciences · 2023Article
- The Role of Cyclic Adenosine Monophosphate (cAMP) in Modulating Glucocorticoid Receptor Signaling and Its Implications on Glucocorticoid-Related Collagen Loss.International journal of molecular sciences · 2023Article
- TargetingJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- Splicing is an alternate oncogenic pathway activation mechanism in glioma.Nature communications · 2022Article
- Review
- Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAFClinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Transcriptional co-activator regulates melanocyte differentiation and oncogenesis by integrating cAMP and MAPK/ERK pathways.Cell reports · 2021Article
- Cyclic adenosine monophosphate (cAMP) signaling in melanocyte pigmentation and melanomagenesis.Pigment cell & melanoma research · 2021Review
- Article
- Mucinous borderline ovarian tumors with BRAFArchives of gynecology and obstetrics · 2020Article
- Targeting B-Raf inhibitor resistant melanoma with novel cell penetrating peptide disrupters of PDE8A - C-Raf.BMC cancer · 2019Article
- The temporal profile of activity-dependent presynaptic phospho-signalling reveals long-lasting patterns of poststimulus regulation.PLoS biology · 2019Article
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Melanocytes use BRAF to activate the MAP kinase (MAPK) pathway because CRAF is inhibited by the cyclic AMP (cAMP) pathway in these cells. By contrast, melanomas harboring Ras mutations use CRAF to activate the MAPK pathway. We describe the molecular mechanism of Raf isoform switching and cAMP pathway disruption, which take place during melanocyte transformation. We show that overactivation of the MAPK pathway, induced by the oncogenic Ras in melanoma, induces constitutive phosphorylation of BRAF on Ser151 by ERK, which inhibits NRAS-BRAF interaction . We also demonstrate that melanoma cells have elevated cAMP phosphodiesterase activity owing to overexpression of the cAMP-specific phosphodiesterase-4 enzymes; this activity inhibits cAMP signaling and allows CRAF reactivation in these cells. Reactivating the cAMP pathway inhibits proliferation and induces apoptosis of Ras-mutated melanoma cells, suggesting a new therapeutic approach for treating melanomas harboring Ras mutations.
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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 OpenQuestion graph.