ArticleOncogene2001
A novel mutation within the extracellular domain of TrkA causes constitutive receptor activation.
Article in Oncogene, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 54 citations in OpenAlex.
- Small-Molecule Trk Agonists: Where Do We Go from Here?Journal of medicinal chemistry · 2025Review
- Molecular basis of VEGFR1 autoinhibition at the plasma membrane.Nature communications · 2024Article
- TrkA Co-Receptors: The Janus Face of TrkA?Cancers · 2023Review
- Intrinsically disordered regions couple the ligand binding and kinase activation of Trk neurotrophin receptors.iScience · 2022Article
- High-affinity TrkA and p75 neurotrophin receptor complexes: A twisted affair.The Journal of biological chemistry · 2022Review
- Structural basis of the transmembrane domain dimerization and rotation in the activation mechanism of the TRKA receptor by nerve growth factor.The Journal of biological chemistry · 2020Article
- Article
- Review
- Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development and Clinical Application.Journal of medicinal chemistry · 2019Article
- NTRK fusion-positive cancers and TRK inhibitor therapy.Nature reviews. Clinical oncology · 2018Review
- Entrectinib: an orally available, selective tyrosine kinase inhibitor for the treatment ofTherapeutics and clinical risk management · 2018Review
- TRKing down an old oncogene in a new era of targeted therapy.Cancer discovery · 2015Review
- Small-molecule modulation of neurotrophin receptors: a strategy for the treatment of neurological disease.Nature reviews. Drug discovery · 2013Review
- An intracellular domain fragment of the p75 neurotrophin receptor (p75(NTR)) enhances tropomyosin receptor kinase A (TrkA) receptor function.The Journal of biological chemistry · 2013Article
- A monovalent agonist of TrkA tyrosine kinase receptors can be converted into a bivalent antagonist.Biochimica et biophysica acta · 2010Article
- Article
- Bivalent peptidomimetic ligands of TrkC are biased agonists and selectively induce neuritogenesis or potentiate neurotrophin-3 trophic signals.ACS chemical biology · 2009Article
- A novel p75 neurotrophin receptor-related protein, NRH2, regulates nerve growth factor binding to the TrkA receptor.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2004Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The TrkA NGF receptor extracellular region contains three leucine repeats flanked by cysteine clusters and two immunoglobulin-like domains that are required for specific ligand binding. Deletion of the immunoglobulin-like domains abolishes NGF binding and causes ligand independent activation of the receptor. Here we report a specific mutation that increases the binding affinity of the TrkA receptor for NGF. A change of proline 203 to alanine (P203A) in the linker region between the leucine repeats and the first Ig-like domain increased NGF binding by decreasing the ligand rate of dissociation. This mutated receptor was appropriately expressed on the cell surface and promoted ligand-independent neurite outgrowth in PC12nnr5 cells. The mutant receptor was capable of spontaneous dimerization and was constitutively phosphorylated in the absence of ligand. Moreover, expression of TrkA-P203A receptor in fibroblasts induced DNA synthesis and transformation and generated tumours in nude mice. These data suggest that domains outside of the immunoglobulin-like structure contribute to ligand binding and constitutive activation of Trk receptors.
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.