ArticleThe Journal of investigative dermatology2016
Phosphoproteomic Analyses of NRAS(G12) and NRAS(Q61) Mutant Melanocytes Reveal Increased CK2α Kinase Levels in NRAS(Q61) Mutant Cells.
Article in The Journal of investigative dermatology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 34 citations in OpenAlex.
- Differential Outcomes in Codon 12/13 and Codon 61Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
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- Modulation of the 14-3-3σ/C-RAF "Auto"inhibited Complex by Molecular Glues.Journal of the American Chemical Society · 2026Article
- Advances in Cutaneous Melanoma Therapy: The Emerging Role of CDK4/6 Inhibitors.Pharmacological research · 2025Review
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- Relative genotoxicity of polycyclic aromatic hydrocarbons inferred from free energy perturbation approaches.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Assessment of RAS-RAF-MAPK Pathway Mutation Status in Healthy Skin, Benign Nevi, and Cutaneous Melanomas: Pilot Study Using Droplet Digital PCR.International journal of molecular sciences · 2024Article
- Mediating kinase activity in Ras-mutant cancer: potential for an individualised approach?Frontiers in pharmacology · 2024Review
- Reclassification ofTherapeutic advances in medical oncology · 2024Article
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- PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma.Life science alliance · 2022Article
- CK2 Regulation: Perspectives in 2021.Biomedicines · 2021Review
- Vulvar Melanoma: Molecular Characteristics, Diagnosis, Surgical Management, and Medical Treatment.American journal of clinical dermatology · 2021Review
- Inhibition of the Myocardin-Related Transcription Factor Pathway Increases Efficacy of Trametinib inCancers · 2021Article
- The effects of mutant Ras proteins on the cell signalome.Cancer metastasis reviews · 2020Review
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- A Comparative Analysis of Individual RAS Mutations in Cancer Biology.Frontiers in oncology · 2019Review
- Cancer-type dependent expression of CK2 transcripts.PloS one · 2017Article
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16 authors at 6 institutions in 3 countries.
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Abstract
In melanoma, mutant and thereby constantly active neuroblastoma rat sarcoma (NRAS) affects 15-20% of tumors, contributing to tumor initiation, growth, invasion, and metastasis. Recent therapeutic approaches aim to mimic RAS extinction by interfering with critical signaling pathways downstream of the mutant protein. This study investigates the phosphoproteome of primary human melanocytes bearing mutations in the two hot spots of NRAS, NRAS(G12) and NRAS(Q61). Stable isotope labeling by amino acids in cell culture followed by mass spectrometry identified 14,155 spectra of 3,371 unique phosphopeptides mapping to 1,159 proteins (false discovery rate < 2%). Data revealed pronounced PI3K/AKT signaling in NRAS(G12V) mutant cells and pronounced mitogen-activated protein kinase (MAPK) signaling in NRAS(Q61L) variants. Computer-based prediction models for kinases involved, revealed that CK2α is significantly overrepresented in primary human melanocytes bearing NRAS(Q61L) mutations. Similar differences were found in human NRAS(Q61) mutant melanoma cell lines that were also more sensitive to pharmacologic CK2α inhibition compared with NRAS(G12) mutant cells. Furthermore, CK2α levels were pronounced in patient samples of NRAS(Q61) mutant melanoma at the mRNA and protein level. The preclinical findings of this study reveal that codon 12 and 61 mutant NRAS cells have distinct signaling characteristics that could allow for the development of more effective, mutation-specific treatment modalities.
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