ArticleProceedings of the National Academy of Sciences of the United States of America1998
Activating mutations in the extracellular domain of the fibroblast growth factor receptor 2 function by disruption of the disulfide bond in the third immunoglobulin-like domain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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.
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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
59 citing papers in PubMed, 187 citations in OpenAlex.
- Quantification of facial skeletal shape variation in fibroblast growth factor receptor-related craniosynostosis syndromes.Birth defects research. Part A, Clinical and molecular teratology · 2014Trial
- Decreased proliferation and altered differentiation in osteoblasts from genetically and clinically distinct craniosynostotic disorders.The American journal of pathology · 1999Trial
- Combining Mendelian Randomization and Experimental Validation to Reveal the Causal Relationship Between Hallux Valgus and Serum Metabolites and to Identify Their Therapeutic Targets and Relevant Components.Food science & nutrition · 2026Article
- FGFR2 residence in primary cilia is necessary for epithelial cell signaling.The Journal of cell biology · 2025Article
- Targeted allele-specificMolecular therapy. Nucleic acids · 2025Article
- Genetic insights into the 'sandwich fusion' subtype of Klippel-Feil syndrome: novel FGFR2 mutations identified by 21 cases of whole-exome sequencing.Orphanet journal of rare diseases · 2024Article
- Oncogenic activation revealed by FGFR2 genetic alterations in intrahepatic cholangiocarcinomas.Cell & bioscience · 2023Article
- Computational and Functional Analyses of HER2 Mutations Reveal Allosteric Activation Mechanisms and Altered Pharmacologic Effects.Cancer research · 2023Article
- Oncogenic RAS Drives Resistance to Pemigatinib in Cholangiocarcinoma Harboring a FGFR2 Delins Disrupting Ligand Binding.JCO precision oncology · 2023Article
- Article
- Oncogenic fusion protein FGFR2-PPHLN1: Requirements for biological activation, and efficacy of inhibitors.Translational oncology · 2020Article
- Genetic background dependent modifiers of craniosynostosis severity.Journal of structural biology · 2020Article
- Fibroblast growth factor signalling in osteoarthritis and cartilage repair.Nature reviews. Rheumatology · 2020Review
- Cranial Neural Crest Cells and Their Role in the Pathogenesis of Craniofacial Anomalies and Coronal Craniosynostosis.Journal of developmental biology · 2020Review
- Article
- Nuclear Fibroblast Growth Factor Receptor Signaling in Skeletal Development and Disease.Current osteoporosis reports · 2019Review
- FGF Signaling in Lung Development and Disease: Human Versus Mouse.Frontiers in genetics · 2019Review
- Neomorphic PDGFRA extracellular domain driver mutations are resistant to PDGFRA targeted therapies.Nature communications · 2018Article
- Mechanisms of receptor tyrosine kinase activation in cancer.Molecular cancer · 2018Review
- FGFR2 mutations and associated clinical observations in two Chinese patients with Crouzon syndrome.Molecular medicine reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Multiple human skeletal and craniosynostosis disorders, including Crouzon, Pfeiffer, Jackson-Weiss, and Apert syndromes, result from numerous point mutations in the extracellular region of fibroblast growth factor receptor 2 (FGFR2). Many of these mutations create a free cysteine residue that potentially leads to abnormal disulfide bond formation and receptor activation; however, for noncysteine mutations, the mechanism of receptor activation remains unclear. We examined the effect of two of these mutations, W290G and T341P, on receptor dimerization and activation. These mutations resulted in cellular transformation when expressed as FGFR2/Neu chimeric receptors. Additionally, in full-length FGFR2, the mutations induced receptor dimerization and elevated levels of tyrosine kinase activity. Interestingly, transformation by the chimeric receptors, dimerization, and enhanced kinase activity were all abolished if either the W290G or the T341P mutation was expressed in conjunction with mutations that eliminate the disulfide bond in the third immunoglobulin-like domain (Ig-3). These results demonstrate a requirement for the Ig-3 cysteine residues in the activation of FGFR2 by noncysteine mutations. Molecular modeling also reveals that noncysteine mutations may activate FGFR2 by altering the conformation of the Ig-3 domain near the disulfide bond, preventing the formation of an intramolecular bond. This allows the unbonded cysteine residues to participate in intermolecular disulfide bonding, resulting in constitutive activation of the 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.