RAS variant signalling
Open accessAbstract
RAS proteins are small GTPases that regulate signalling networks that control cellular proliferation and survival. They are frequently mutated in cancer and a commonly occurring group of developmental disorders called RASopathies. We discuss recent findings describing how RAS isoforms and different activating mutations differentially contribute to normal and disease-associated biology and the mechanisms that have been proposed to underpin this.
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Somatic RAS mutations are primarily gain-of-function missense alterations at codons 12, 13, or 61 that impair GTP hydrolysis to favor the active state, resulting in increased downstream signaling linked to proliferation, survival, and tumorigenesis.
“Somatic RAS mutations were the first oncogenic mutations identified in human cancers (1) and are primarily comprised of gain-of-function missense alterations at codons 12, 13, or 61 that impair GTP hydrolysis to favor the protein's active state, resulting in increased activation of downstream signaling pathways linked to cell proliferation, cell survival, and tumorigenesis (2).”
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- Authors
- Mo, S. P., Coulson, J. M., & Prior, I. A.
- Affiliations
- University of Liverpool (GB)
- Corresponding author
- Prior, Ian A.
- Venue
- Biochemical Society Transactions
- Publisher
- Portland Press Ltd.
- Published
- 2018-10-04
- Volume
- 46
- Issue
- 5
- Pages
- 1325-1332
- ISSN
- 0300-5127 (ISSN-L)
- 1470-8752
- PMC
- PMC6195641
- OpenAlex
- W2895665486
- Cited by
- 85
- References
- 65
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 13 · 2023: 12 · 2022: 20 · 2021: 11 · 2020: 14 · 2019: 5
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Biochemical Society Transactions (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (WT109309)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Ras proteins, small GTPases, Ras isoforms, RAS mutations, RASopathies, cancer, cell proliferation, cell survival, signaling networks, disease-associated mutations
- MeSH terms
- Animals, Cell Membrane, Developmental Disabilities, Humans, Mutation, Neoplasms, Signal Transduction, ras Proteins, Protein Isoforms, Cell Proliferation, Protein Multimerization
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