ReviewCancer science2008
Regulation of growth factor signaling by FRS2 family docking/scaffold adaptor proteins.
Review in Cancer science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
137 citing papers in PubMed, 1 synthesis or guideline pooled it, 263 citations in OpenAlex.
- Safety and efficacy of the pan-FGFR inhibitor erdafitinib in advanced urothelial carcinoma and other solid tumors: A systematic review and meta-analysis.Frontiers in oncology · 2022Pooled it
- Targeting receptor tyrosine kinases: from molecular mechanisms to clinical therapeutics.Signal transduction and targeted therapy · 2026Review
- State-Dependent FGF Signaling in Satellite Cell-Mediated Skeletal Muscle Regeneration and Pathological Remodeling.Biomolecules · 2026Review
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
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- Fibroblast growth factor receptor substrate 2 interactome mapping reveals novel candidate interactors associated with migration and invasion.Cell communication and signaling : CCS · 2026Article
- FGF family in health and disease.Molecular biomedicine · 2026Review
- FGF4 activates FGFR1 - PI3K/AKT signaling to enhance Clec10a-mediated intracellular myelin debris processing and promote spinal cord repair.Journal of neuroinflammation · 2026Article
- FGFR signaling and apoptotic regulation in cancer: links to immune evasion, therapeutic resistance, and treatment re-engagement.Frontiers in immunology · 2026Review
- Unraveling the FGFR-RNA splicing axis: Mechanisms, oncogenic crosstalks and innovations for therapeutic purpose.Acta pharmaceutica Sinica. B · 2026Review
- Droplet digital PCR assay for precise determination of FRS2 gene copy number in bladder cancer.BMC cancer · 2025Article
- FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025Review
- Clinical advances and challenges in targeting FGF/FGFR signaling in lung cancer.Molecular cancer · 2024Review
- Targeting the cancer cells and cancer-associated fibroblasts with next-generation FGFR inhibitors in prostate cancer co-culture models.Cancer medicine · 2024Article
- Quantitative and qualitative differences in the activation of a fibroblast growth factor receptor by different FGF ligands.Cytokine & growth factor reviews · 2024Review
- Efficient improvement of the proliferation, differentiation, and anti-arthritic capacity of mesenchymal stem cells by simply culturing on the immobilized FGF2 derived peptide, 44-ERGVVSIKGV-53.Journal of advanced research · 2024Article
- Article
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- ANRIL: A Long Noncoding RNA in Age-related Diseases.Mini reviews in medicinal chemistry · 2024Review
- Quantification of ligand and mutation-induced bias in EGFR phosphorylation in direct response to ligand binding.Nature communications · 2023Article
77 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The FRS2 family of adaptor/scaffold proteins has two members, FRS2alpha and FRS2beta. Both proteins contain N-terminal myristylation sites for localization on the plasma membrane and a PTB domain for binding to limited species of receptor tyrosine kinases (RTKs), including the FGF receptor, the neurotophin receptor, RET, and ALK. Activation of these RTKs allows FRS2 proteins to become phosphorylated of tyrosine residues and then bind to Grb2 and Shp2, a SH2 domain-containing adaptor and a tyrosine phosphatase, respectively. Subsequently, Shp2 activates a Ras/ERK pathway and Grb2 activates a Ras/ERK, phosphatidyl inositol (PI)-3 kinase and ubiquitination/degradation pathways by binding to SOS, Gab1, and Cbl via the SH3 domains of Grb2. FRS2alpha acts as 'a conning center' in FGF signaling mainly because it induces sustained levels of activation of ERK via Shp2-binding sites and Grb2-binding sites, though the contribution of the former is greater. Indeed, FRS2alpha knockout mice and mice with mutated Shp2-binding sites exhibit a variety of phenotypes due to defects in FGF signaling in vivo. Although FRS2beta binds to the EGF receptor, it does not induce tyrosine phosphorylation on the receptor. Instead, it inhibits EGF signaling, resulting in inhibition of EGF-induced cell proliferation and cell transformation. Based on these findings, the involvement of FRS2 proteins in tumorigenesis should be studied extensively to be validated as candidate biomarkers for the effectiveness of treatments targeting RTKs such as the FGF receptor and EGF receptor.
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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.