ArticleThe EMBO journal1996
Constitutive activation of fibroblast growth factor receptor 3 by the transmembrane domain point mutation found in achondroplasia.
Article in The EMBO journal, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 303 citations in OpenAlex.
- Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type natriuretic peptide prodrug, TransCon CNP.British journal of clinical pharmacology · 2022Trial
- [Clinical features and variant spectrum ofZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
- Expert Consensus on the Diagnosis and Treatment of FGFR Gene-Altered Solid Tumors.Global medical genetics · 2024Review
- A polarized FGF8 source specifies frontotemporal signatures in spatially oriented cell populations of cortical assembloids.Nature methods · 2024Article
- The roles of FGFR3 and c-MYC in urothelial bladder cancer.Discover oncology · 2024Review
- Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.Cell discovery · 2024Review
- Alteration of major venous drainage routes in a patient with achondroplasia after ventriculoperitoneal shunt placement.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Article
- New insights in craniovertebral junction MR changes leading to stenosis in children with achondroplasia.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2022Article
- Psychomotor Delay in a Child withGlobal medical genetics · 2021Article
- Advantages and Disadvantages of Different Treatment Methods in Achondroplasia: A Review.International journal of molecular sciences · 2021Review
- Typical achondroplasia secondary to a unique insertional variant of FGFR3 with in vitro demonstration of its effect on FGFR3 function.American journal of medical genetics. Part A · 2021Article
- Whole-exome sequencing identified a novel variant in an Iranian patient affected by pycnodysostosis.Molecular genetics & genomic medicine · 2020Article
- Membrane receptor activation mechanisms and transmembrane peptide tools to elucidate them.The Journal of biological chemistry · 2020Review
- Obesity in achondroplasia patients: from evidence to medical monitoring.Orphanet journal of rare diseases · 2019Review
- A Novel FGFR3 Splice Variant Preferentially Expressed in African American Prostate Cancer Drives Aggressive Phenotypes and Docetaxel Resistance.Molecular cancer research : MCR · 2019Article
- Achondroplasia: a comprehensive clinical review.Orphanet journal of rare diseases · 2019Review
- Targeting Cellular Trafficking of Fibroblast Growth Factor Receptors as a Strategy for Selective Cancer Treatment.Journal of clinical medicine · 2018Review
- Integrated bioinformatic analysis of microarray data reveals shared gene signature between MDS and AML.Oncology letters · 2018Article
- Early postnatal soluble FGFR3 therapy prevents the atypical development of obesity in achondroplasia.PloS one · 2018Article
- Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Achondroplasia, the most common genetic form of dwarfism, is an autosomal dominant disorder whose underlying mechanism is a defect in the maturation of the cartilage growth plate of long bones. Achondroplasia has recently been shown to result from a Gly to Arg substitution in the transmembrane domain of the fibroblast growth factor receptor 3 (FGFR3), although the molecular consequences of this mutation have not been investigated. By substituting the transmembrane domain of the Neu receptor tyrosine kinase with the transmembrane domains of wild-type and mutant FGFR3, the Arg380 mutation in FGFR3 is shown to activate both the kinase and transforming activities of this chimeric receptor. Residues with side chains capable of participating in hydrogen bond formation, including Glu, Asp, and to a lesser extent, Gln, His and Lys, were able to substitute for the activating Arg380 mutation. The Arg380 point mutation also causes ligand-independent stimulation of the tyrosine kinase activity of FGFR3 itself, and greatly increased constitutive levels of phosphotyrosine on the receptor. These results suggest that the molecular basis of achondroplasia is unregulated signal transduction through FGFR3, which may result in inappropriate cartilage growth plate differentiation and thus abnormal long bone development. Achondroplasia may be one of the number of cogenital disorders where constitutive activation of a member of the FGFR family leads to development abnormalities.
Indexed as
Identifiers
8599935PMC449970W1570281893What 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.