ArticleThe Journal of cell biology2002
Mechanisms through which Sos-1 coordinates the activation of Ras and Rac.
Article in The Journal of cell biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 192 citations in OpenAlex.
- Polarized SOS activity orchestrates FGF-directed cell migration in vivo.Current biology : CB · 2026Article
- SOS1: tracking the evolving path from promising to actionable therapeutic target in RAS-dependent cancers.Molecular cancer · 2026Review
- LRRC8A-containing anion channels promote glioblastoma proliferation via a WNK1/mTORC2-dependent mechanism.The Journal of physiology · 2026Article
- Decoding Rho GTPase signalling networks in directed cell migration.Frontiers in cell and developmental biology · 2026Review
- The Slit-Robo signalling pathway in nervous system development: a comparative perspective from vertebrates and invertebrates.Open biology · 2025Review
- SOS1 inhibitor BI-3406 shows in vivo antitumor activity akin to genetic ablation and synergizes with a KRASProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sos1 ablation alters focal adhesion dynamics and increases Mmp2/9-dependent gelatinase activity in primary mouse embryonic fibroblasts.Cell communication and signaling : CCS · 2025Article
- KRAS inhibitors: resistance drivers and combinatorial strategies.Trends in cancer · 2025Review
- The Role of the Swollen State in Cell Proliferation.The Journal of membrane biology · 2025Review
- Standardized Parts for Activation of Small GTPase Signaling in Living Cells.Angewandte Chemie (International ed. in English) · 2024Article
- Systems Biology Methods via Genome-Wide RNA Sequences to Investigate Pathogenic Mechanisms for Identifying Biomarkers and Constructing a DNN-Based Drug-Target Interaction Model to Predict Potential Molecular Drugs for Treating Atopic Dermatitis.International journal of molecular sciences · 2024Article
- Mechanically operated signalling scaffolds.Biochemical Society transactions · 2024Review
- Standardized Parts for Activation of Small GTPase Signaling in Living Cells.bioRxiv : the preprint server for biology · 2024Article
- A planar polarized MYO6-DOCK7-RAC1 axis promotes tissue fluidification in mammary epithelia.Cell reports · 2023Article
- Root-Knot Disease Suppression in Eggplant Based on Three Growth Ages ofMicroorganisms · 2022Article
- Allosteric regulation of GRB2 modulates RAS activation.Small GTPases · 2022Article
- Clinics and genetic background of hereditary gingival fibromatosis.Orphanet journal of rare diseases · 2021Review
- SOS2 Comes to the Fore: Differential Functionalities in Physiology and Pathology.International journal of molecular sciences · 2021Review
- The Crossroads between RAS and RHO Signaling Pathways in Cellular Transformation, Motility and Contraction.Genes · 2021Review
- Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling from receptor tyrosine kinases (RTKs)* requires the sequential activation of the small GTPases Ras and Rac. Son of sevenless (Sos-1), a bifunctional guanine nucleotide exchange factor (GEF), activates Ras in vivo and displays Rac-GEF activity in vitro, when engaged in a tricomplex with Eps8 and E3b1-Abi-1, a RTK substrate and an adaptor protein, respectively. A mechanistic understanding of how Sos-1 coordinates Ras and Rac activity is, however, still missing. Here, we demonstrate that (a) Sos-1, E3b1, and Eps8 assemble into a tricomplex in vivo under physiological conditions; (b) Grb2 and E3b1 bind through their SH3 domains to the same binding site on Sos-1, thus determining the formation of either a Sos-1-Grb2 (S/G) or a Sos-1-E3b1-Eps8 (S/E/E8) complex, endowed with Ras- and Rac-specific GEF activities, respectively; (c) the Sos-1-Grb2 complex is disrupted upon RTKs activation, whereas the S/E/E8 complex is not; and (d) in keeping with the previous result, the activation of Ras by growth factors is short-lived, whereas the activation of Rac is sustained. Thus, the involvement of Sos-1 at two distinct and differentially regulated steps of the signaling cascade allows for coordinated activation of Ras and Rac and different duration of their signaling within the cell.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.