The DOI matches its Crossref record; 82 of the 82 references it cites were found in a registry or an index.
Signaling Specificity by Ras Family GTPases Is Determined by the Full Spectrum of Effectors They Regulate
Open accessAbstract
Ras family GTPases (RFGs) regulate signaling pathways that control multiple biological processes. How signaling specificity among the closely related family members is achieved is poorly understood. We have taken a proteomics approach to signaling by RFGs, and we have analyzed interactions of a panel of RFGs with a comprehensive group of known and potential effectors. We have found remarkable differences in the ability of RFGs to regulate the various isoforms of known effector families. We have also identified several proteins as novel effectors of RFGs with differential binding specificities to the various RFGs. We propose that specificity among RFGs is achieved by the differential regulation of combinations of effector families as well as by the selective regulation of different isoforms within an effector family. An understanding of this new level of complexity in the signaling pathways regulated by RFGs is necessary to understand how they carry out their many cellular functions. It will also likely have critical implications in the treatment of human diseases such as cancer.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“While MRAS shares approximately 50% sequence identity with other RAS isoforms and can interact with some of the common RAS effectors and regulators, such as RAF, PI3K, RalGDS and SOS38,50,51”
From Co-targeting SOS1 enhances the antitumor effects of KRASG12C inhibitors by addressing intrinsic and acquired resistance (2024) · cites this paper as [50]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
ras oncogenes in human cancer: a review.
Bos, J. L. (1989) · PubMed · Cited by 5,061
Takai, Y., Sasaki, T., & Matozaki, T. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.1.153 · Cited by 2,511
Katso, R., Okkenhaug, K., Ahmadi, K., White, S., Timms, J. F., & Waterfield, M. D. (2001) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.17.1.615 · Cited by 1,234
FUNCTION AND REGULATION OF RAS
Lowy, D. R., & Willumsen, B. M. (1993) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.62.070193.004223 · Cited by 1,164
Dammann, R., Li, C., Yoon, J., Chin, P. L., Bates, S., & Pfeifer, G. P. (2000) · Nature Genetics · doi:10.1038/77083 · Cited by 1,064
Woods, D. B., Parry, D., Cherwinski, H. M., Bosch, E., Lees, E. M., & McMahon, M. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.9.5598 · Cited by 639
Rap1 signalling: adhering to new models
Bos, J. L., de Rooij, J., & Reedquist, K. A. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35073073 · Cited by 625
A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK
Enserink, J. M., Christensen, A. E., de Rooij, J., van Triest, M., Schwede, F., Genieser, H. G., Døskeland, S. O., Blank, J. L., & Bos, J. L. (2002) · Nature Cell Biology · doi:10.1038/ncb874 · Cited by 625
Crystal Structure and Functional Analysis of Ras Binding to Its Effector Phosphoinositide 3-Kinase γ
Pacold, M. E., Suire, S., Perišić, O., Lara‐González, S., Davis, C. T., Walker, E. H., Hawkins, P. T., Stephens, L., Eccleston, J. F., & Williams, R. L. (2000) · Cell · doi:10.1016/s0092-8674(00)00196-3 · Cited by 611
Phosphatidylinositol-3-OH kinases are Rab5 effectors
Christoforidis, S., Miaczynska, M., Ashman, K., Wilm, M., Zhao, L., Yip, S.-C., Waterfield, M. D., Backer, J. M., & Zerial, M. (1999) · Nature Cell Biology · doi:10.1038/12075 · Cited by 559
Cited by
Sorted by citations
Ras, PI(3)K and mTOR signalling controls tumour cell growth
Shaw, R. J., & Cantley, L. C. (2006) · Nature · doi:10.1038/nature04869 · Cited by 2,019
“However, it is not clear whether the Raf–ERK pathway is the most critical mediator of Ras-dependent tumorigenesis in all cell types; several other Ras effectors have been identified in the past ten year”
BackgroundRAS Proteins and Their Regulators in Human Disease
Simanshu, D. K., Nissley, D. V., & McCormick, F. (2017) · Cell · doi:10.1016/j.cell.2017.06.009 · Cited by 1,943
Self-citationPI3K and cancer: lessons, challenges and opportunities
Fruman, D. A., & Rommel, C. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4204 · Cited by 1,766
The emerging mechanisms of isoform-specific PI3K signalling
Vanhaesebroeck, B., Guillermet-Guibert, J., Graupera, M., & Bilanges, B. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2882 · Cited by 1,767
“, and the Ras family member TC21 (also known as RRAS2) may have a role in the activation of p110”
BackgroundPI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting
Thorpe, L. M., Yuzugullu, H., & Zhao, J. J. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3860 · Cited by 1,405
Metadata
- Authors
- Rodriguez-Viciana, P., Sabatier, C., & McCormick, F.
- Affiliations
- Cancer Research Institute and Comprehensive Cancer Center, University of California
- University of California, San Francisco (US)
- Corresponding author
- McCormick, Frank
- ORCID
- McCormick, Frank
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-06
- Volume
- 24
- Issue
- 11
- Pages
- 4943-4954
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC416418
- OpenAlex
- W2165023373
- Cited by
- 327
- References
- 81
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 16 · 2023: 5 · 2022: 7 · 2021: 12 · 2020: 5 · 2019: 8 · 2018: 18 · 2017: 10 · 2016: 12 · 2015: 12 · 2014: 13 · 2013: 22 · 2012: 24
- FWCI
- 7.36
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- 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 › Protein Tyrosine Phosphatases
- Keywords
- Ras family GTPases, signaling specificity, effector proteins, protein-protein interaction, signaling pathways, cancer
- MeSH terms
- Humans, Substrate Specificity, Protein Structure, Tertiary, ras Proteins, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-raf, Protein Isoforms, GTP Phosphohydrolases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
