ArticleThe Journal of cell biology2013
Grb2 controls phosphorylation of FGFR2 by inhibiting receptor kinase and Shp2 phosphatase activity.
Article in The Journal of cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The trial behind it
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
49 citing papers in PubMed, 87 citations in OpenAlex.
- FGF family in health and disease.Molecular biomedicine · 2026Review
- Design and synthesis of an erdafitinib-based selective FGFR2 degrader.Beilstein journal of organic chemistry · 2026Article
- CBX2 promoted oral squamous cell carcinoma via increasing CEP55/NF-κB/METTL3/SHP2 signaling induced metastasis/proliferation and angiogenesis.Scientific reports · 2025Article
- FGFR2 residence in primary cilia is necessary for epithelial cell signaling.The Journal of cell biology · 2025Article
- Article
- Phosphoproteomic response to epidermal growth factor in native rat inner medullary collecting duct.American journal of physiology. Renal physiology · 2025Article
- Targeting ERBB3 and AKT to overcome adaptive resistance in EML4-ALK-driven non-small cell lung cancer.Cell death & disease · 2024Article
- The Caenorhabditis elegans protein SOC-3 permits an alternative mode of signal transduction by the EGL-15 FGF receptor.Developmental biology · 2024Article
- GRB2 stabilizes RAD51 at reversed replication forks suppressing genomic instability and innate immunity against cancer.Nature communications · 2024Article
- The Configuration of GRB2 in Protein Interaction and Signal Transduction.Biomolecules · 2024Review
- Next-Cell Hypothesis: Mechanism of Obesity-Associated Carcinogenesis.Advances in experimental medicine and biology · 2024Review
- The combined action of the intracellular regions regulates FGFR2 kinase activity.Communications biology · 2023Article
- FRS2-independent GRB2 interaction with FGFR2 is not required for embryonic development.bioRxiv : the preprint server for biology · 2023Article
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
- 'Cloudbuster': a Python-based open source application for three-dimensional reconstruction and quantification of stacked biological imaging samples.Interface focus · 2022Article
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Receptor tyrosine kinases regulate signal transduction through a liquid-liquid phase separated state.Molecular cell · 2022Article
- Expanding the Disorder-Function Paradigm in the C-Terminal Tails of Erbbs.Biomolecules · 2021Review
- GRB2 enforces homology-directed repair initiation by MRE11.Science advances · 2021Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Constitutive receptor tyrosine kinase phosphorylation requires regulation of kinase and phosphatase activity to prevent aberrant signal transduction. A dynamic mechanism is described here in which the adaptor protein, growth factor receptor-bound protein 2 (Grb2), controls fibroblast growth factor receptor 2 (FGFR2) signaling by regulating receptor kinase and SH2 domain-containing protein tyrosine phosphatase 2 (Shp2) phosphatase activity in the absence of extracellular stimulation. FGFR2 cycles between its kinase-active, partially phosphorylated, nonsignaling state and its Shp2-dephosphorylated state. Concurrently, Shp2 cycles between its FGFR2-phosphorylated and dephosphorylated forms. Both reciprocal activities of FGFR2 and Shp2 were inhibited by binding of Grb2 to the receptor. Phosphorylation of Grb2 by FGFR2 abrogated its binding to the receptor, resulting in up-regulation of both FGFR2's kinase and Shp2's phosphatase activity. Dephosphorylation of Grb2 by Shp2 rescued the FGFR2-Grb2 complex. This cycling of enzymatic activity results in a homeostatic, signaling-incompetent state. Growth factor binding perturbs this background cycling, promoting increased FGFR2 phosphorylation and kinase activity, Grb2 dissociation, and downstream signaling. Grb2 therefore exerts constitutive control over the mutually dependent activities of FGFR2 and Shp2.
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What OpenQuestion holds
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.