Signaling Specificity by Ras Family GTPases Is Determined by the Full Spectrum of Effectors They Regulate
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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.
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MRAS shares approximately 50% sequence identity with other RAS isoforms and can interact with some common RAS effectors and regulators, such as RAF, PI3K, RalGDS and SOS.
“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]
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- 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
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