ArticleMolecular and cellular biology2000
The transmembrane mutation G380R in fibroblast growth factor receptor 3 uncouples ligand-mediated receptor activation from down-regulation.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
47 citing papers in PubMed, 140 citations in OpenAlex.
- Article
- [Clinical features and variant spectrum ofZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
- Gene Dosage Sensitivity and Human Genetic Diseases.Journal of inherited metabolic disease · 2025Review
- A polarized FGF8 source specifies frontotemporal signatures in spatially oriented cell populations of cortical assembloids.Nature methods · 2024Article
- Severe achondroplasia due to two de novo variants in the transmembrane domain of FGFR3 on the same allele: A case report.Molecular genetics & genomic medicine · 2020Article
- In vitro and in vivo characterization of Recifercept, a soluble fibroblast growth factor receptor 3, as treatment for achondroplasia.PloS one · 2020Article
- The evolving therapeutic landscape of genetic skeletal disorders.Orphanet journal of rare diseases · 2019Review
- Mouse Models of Syndromic Craniosynostosis.Molecular syndromology · 2019Review
- Noonan syndrome-causing SHP2 mutants impair ERK-dependent chondrocyte differentiation during endochondral bone growth.Human molecular genetics · 2018Article
- Increased FGF8 signaling promotes chondrogenic rather than osteogenic development in the embryonic skull.Disease models & mechanisms · 2018Article
- A novel S269C mutation in fibroblast growth factor receptor 3 in a Japanese child with hypochondroplasia.Human genome variation · 2018Article
- Molecular therapeutic strategies for FGFR3 gene-related skeletal dysplasia.Journal of molecular medicine (Berlin, Germany) · 2017Review
- Impairment of the transition from proliferative stage to prehypertrophic stage in chondrogenic differentiation of human induced pluripotent stem cells harboring the causative mutation of achondroplasia in fibroblast growth factor receptor 3.Regenerative therapy · 2017Article
- Current Care and Investigational Therapies in Achondroplasia.Current osteoporosis reports · 2017Review
- Achondroplasia: Development, pathogenesis, and therapy.Developmental dynamics : an official publication of the American Association of Anatomists · 2017Review
- Genome-wide association analysis identifies genetic correlates of immune infiltrates in solid tumors.PloS one · 2017Article
- Germline Stem Cell Competition, Mutation Hot Spots, Genetic Disorders, and Older Fathers.Annual review of genomics and human genetics · 2016Review
- Tyrosine Kinase Receptor Landscape in Lung Cancer: Therapeutical Implications.Disease markers · 2016Review
- Fibroblast growth factor receptor signaling in hereditary and neoplastic disease: biologic and clinical implications.Cancer metastasis reviews · 2015Review
- The impact of polyphenols on chondrocyte growth and survival: a preliminary report.Food & nutrition research · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A point mutation, Gly380Arg, in the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3) leads to achondroplasia, the most common form of genetic dwarfism in humans. This substitution was suggested to enhance mutant receptor dimerization, leading to constitutive, ligand-independent activation. We found that dimerization and activation of the G380R mutant receptor are predominantly ligand dependent. However, using both transient and stable transfections, we found significant overexpression only of the mutant receptor protein. Metabolic pulse-chase experiments, cell surface labeling, and kinetics of uptake of radiolabeled ligand demonstrated a selective delay in the down-regulation of the mutant receptor. Moreover, this receptor was now resistant to ligand-mediated internalization, even at saturating ligand concentrations. Finally, transgenic mice expressing the human G380R mutant receptor under the mouse receptor transcriptional control demonstrated a markedly expanded area of FGFR3 immunoreactivity within their epiphyseal growth plates, compatible with an in vivo defect in receptor down-regulation. We propose that the achondroplasia mutation G380R uncouples ligand-mediated receptor activation from down-regulation at a site where the levels and kinetics of FGFR3 signals are crucial for chondrocyte maturation and bone formation.
Indexed as
Identifiers
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.