ArticleNature structural & molecular biology2014
Competition between Grb2 and Plcγ1 for FGFR2 regulates basal phospholipase activity and invasion.
Article in Nature structural & molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- FGFR1 signaling in rheumatoid arthritis: Mechanisms of bone destruction and therapeutic targeting (Review).International journal of molecular medicine · 2026Review
- FGF family in health and disease.Molecular biomedicine · 2026Review
- Generation of human induced pluripotent stem cell lines from patients with FGFR2-linked syndromic craniosynostosis.Disease models & mechanisms · 2025Article
- Review
- Probing phosphorylation events in biological membranes: The transducer function.Biochimica et biophysica acta. Biomembranes · 2024Review
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- Quantitative assessment of ligand bias from bias plots: The bias coefficient "kappa".Biochimica et biophysica acta. General subjects · 2023Article
- The Grb2 splice variant, Grb3-3, is a negative regulator of RAS activation.Communications biology · 2022Article
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Expanding the Disorder-Function Paradigm in the C-Terminal Tails of Erbbs.Biomolecules · 2021Review
- Probing low-copy-number proteins in single living cells using single-cell plasmonic immunosandwich assays.Nature protocols · 2021Article
- Grb2 binding induces phosphorylation-independent activation of Shp2.Communications biology · 2021Article
- Composition of receptor tyrosine kinase-mediated lipid micro-domains controlled by adaptor protein interaction.Scientific reports · 2021Article
- FGF, Mechanism of Action, Role in Parkinson's Disease, and Therapeutics.Frontiers in pharmacology · 2021Review
- Phenotypic Heterogeneity in Tumor Progression, and Its Possible Role in the Onset of Cancer.Frontiers in genetics · 2020Review
- Structural basis for the activation of PLC-γ isozymes by phosphorylation and cancer-associated mutations.eLife · 2019Article
- Epstein-Barr virus microRNAs regulate B cell receptor signal transduction and lytic reactivation.PLoS pathogens · 2019Article
- Regulation of FGF10 Signaling in Development and Disease.Frontiers in genetics · 2018Review
- TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p.Nature communications · 2017Article
- Article
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11 authors at 2 institutions in 1 country.
Funding
Abstract
FGFR2-expressing human cancer cells with low concentrations of the adaptor protein Grb2 show high prevalence for metastatic outcome. In nonstimulated cells, the SH3 domain (and not the SH2 domains) of Plcγ1 directly competes for a binding site at the very C terminus of FGFR2 with the C-terminal SH3 domain of Grb2. Reduction of Grb2 concentration permits Plcγ1 access to the receptor. Recruitment of Plcγ1 in this way is sufficient to upregulate phospholipase activity. This results in elevated phosphatidylinositol 4,5-bisphosphate turnover and intracellular calcium levels, thus leading to increased cell motility and promotion of cell-invasive behavior in the absence of extracellular receptor stimulation. Therefore, metastatic outcome can be dictated by the constitutive competition between Grb2 and Plcγ1 for the phosphorylation-independent binding site on FGFR2.
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Registered trials
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.