ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
Transactivation of Trk neurotrophin receptors by G-protein-coupled receptor ligands occurs on intracellular membranes.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 255 citations in OpenAlex.
- Transactivation of receptor tyrosine kinases by purinergic P2Y and adenosine receptors.Purinergic signalling · 2023Pooled it
- TrkA abundance is increased in cutaneous nerves in bortezomib-induced neuropathy.Brain pathology (Zurich, Switzerland) · 2026Article
- Decoding BDNF in neurodevelopmental, neurodegenerative, and neurological disorders: mechanisms and therapeutic perspectives.Molecular biology reports · 2026Review
- Retrograde transport of neurotrophin receptor TrkB-FL induced by excitotoxicity regulates Golgi stability and is a target for stroke neuroprotection.Cell death & disease · 2025Article
- Atypical cellular responses mediated by intracellular constitutive active TrkB (NTRK2) kinase domains and a solely intracellular NTRK2-fusion oncogene.Cancer gene therapy · 2024Article
- Neurotrophins and Their Receptors: BDNF's Role in GABAergic Neurodevelopment and Disease.International journal of molecular sciences · 2024Review
- Review
- Adenosinergic System and BDNF Signaling Changes as a Cross-Sectional Feature of RTT: Characterization ofInternational journal of molecular sciences · 2023Article
- Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury.International journal of molecular sciences · 2023Review
- The LRP1/CD91 ligands, tissue-type plasminogen activator, αScientific reports · 2022Article
- Transactivation of TrkB Receptors by Oxytocin and Its G Protein-Coupled Receptor.Frontiers in molecular neuroscience · 2022Article
- Roles of Endomembrane Alkali Cation/Proton Exchangers in Synaptic Function and Neurodevelopmental Disorders.Frontiers in physiology · 2022Review
- Article
- Combined kinesin-1 and kinesin-3 activity drives axonal trafficking of TrkB receptors in Rab6 carriers.Developmental cell · 2021Article
- BDNF signaling during the lifetime of dendritic spines.Cell and tissue research · 2020Review
- Neuroprotection by Neurotropin through Crosstalk of Neurotrophic and Innate Immune Receptors in PC12 Cells.International journal of molecular sciences · 2020Article
- Review
- Brain-derived neurotrophic factor (BDNF) and TrkB hippocampal gene expression are putative predictors of neuritic plaque and neurofibrillary tangle pathology.Neurobiology of disease · 2019Article
- PAC1 regulates receptor tyrosine kinase transactivation in a reactive oxygen species-dependent manner.Peptides · 2019Article
- Early Downregulation of p75Molecular neurobiology · 2019Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Neurotrophins, such as NGF and BDNF, activate Trk receptor tyrosine kinases through receptor dimerization at the cell surface followed by autophosphorylation and intracellular signaling. It has been shown that activation of Trk receptor tyrosine kinases can also occur via a G-protein-coupled receptor (GPCR) mechanism, without involvement of neurotrophins. Two GPCR ligands, adenosine and pituitary adenylate cyclase-activating polypeptide (PACAP), can activate Trk receptor activity to increase the survival of neural cells through stimulation of Akt activity. To investigate the mechanism of Trk receptor transactivation, we have examined the localization of Trk receptors in PC12 cells and primary neurons after treatment with adenosine agonists and PACAP. In contrast to neurotrophin treatment, Trk receptors were sensitive to transcriptional and translational inhibitors, and they were found predominantly in intracellular locations particularly associated with Golgi membranes. Biotinylation and immunostaining experiments confirm that most of the transactivated Trk receptors are found in intracellular membranes. These results indicate that there are alternative modes of activating Trk receptor tyrosine kinases in the absence of neurotrophin binding at the cell surface and that receptor signaling may occur and persist inside of neuronal cells.
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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.