Activation of RalA is critical for Ras-induced tumorigenesis of human cells
Open accessAbstract
RalGEFs were recently shown to be critical for Ras-mediated transformed and tumorigenic growth of human cells. We now show that the oncogenic activity of these proteins is propagated by activation of one RalGEF substrate, RalA, but blunted by another closely related substrate, RalB, and that the oncogenic signaling requires binding of the RalBP1 and exocyst subunit effector proteins. Knockdown of RalA expression impeded, if not abolished, the ability of human cancer cells to form tumors. RalA was also commonly activated in a panel of cell lines from pancreatic cancers, a disease characterized by activation of Ras. Activation of RalA signaling thus appears to be a critical step in Ras-induced transformation and tumorigenesis of human cells.
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Active Ral activates cellular processes through effectors including RalBP1, Sec5/Exo85, filamin, and phospholipase D1.
“Active Ral activates cellular processes through effectors including Ral Binding Protein 1 (RalBP1, RLIP76 or RIP17), Sec5/Exo85, filamin, and phospholipase D18–10.”
From Discovery and characterization of small molecules that target the GTPase Ral (2014) · cites this paper as [9]
The passages on RalA effector binding identify RalBP1, filamin, PLD1, and the exocyst subunits Sec5 and Exo84. The claim says “Sec5/Exo85,” but our copy names Exo84, not Exo85. (LLM, conf=0.86)
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- Authors
- Lim, K.-H., Baines, A. T., Fiordalisi, J. J., Shipitsin, M., Feig, L. A., Cox, A. D., Der, C. J., & Counter, C. M.
- Affiliations
- Duke Medical Center (US)
- University of North Carolina at Chapel Hill (US)
- Tufts University (US)
- Corresponding author
- Counter, Christopher M.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 7
- Issue
- 6
- Pages
- 533-545
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W1982967858
- Cited by
- 355
- References
- 2
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 12 · 2022: 10 · 2021: 12 · 2020: 16 · 2019: 20 · 2018: 13 · 2017: 20 · 2016: 18 · 2015: 18 · 2014: 17 · 2013: 20 · 2012: 18
- FWCI
- 7.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- Lustgarten Foundation
- National Institutes of Health (5r01ca042978-30)
- National Cancer Institute (CA42978, CA94184, R01CA094184)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- RalA, RalB, Ras signaling, oncogenic transformation, carcinogenesis, RALBP1, exocyst, pancreatic cancer
- MeSH terms
- Animals, Carrier Proteins, Cell Line, Cell Transformation, Neoplastic, Guanosine Triphosphate, Humans, Neoplasm Transplantation, Neoplasms, Pancreatic Neoplasms, Protein Binding, Transfection, Gene Expression, Proto-Oncogene Proteins p21(ras), Mice, SCID, ATP-Binding Cassette Transporters, GTPase-Activating Proteins, ral GTP-Binding Proteins, ral Guanine Nucleotide Exchange Factor, rho GTP-Binding Proteins, Protein Transport, Vesicular Transport Proteins, RNA, Small Interfering, Cell Line, Tumor, Cell Proliferation, Mice
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