ArticleThe Journal of biological chemistry2008
Proneurotrophins require endocytosis and intracellular proteolysis to induce TrkA activation.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 56 citations in OpenAlex.
- VEGF and Neurotrophins Interaction in the Retinal Neurovascular Unit Homeostasis: A Target for Ocular Disease Treatment and Management.Pharmaceutical research · 2026Review
- ProNGF processing in adult rat tissues and bioactivity of NGF prodomain peptides.FEBS open bio · 2024Article
- Astrocytic microdomains from mouse cortex gain molecular control over long-term information storage and memory retention.Communications biology · 2021Article
- Bioenergetic Requirements and Spatiotemporal Profile of Nerve Growth Factor Induced PI3K-Akt Signaling Along Sensory Axons.Frontiers in molecular neuroscience · 2021Article
- Loss of TrkB Signaling Due to Status Epilepticus Induces a proBDNF-Dependent Cell Death.Frontiers in cellular neuroscience · 2019Article
- ProNGF and Neurodegeneration in Alzheimer's Disease.Frontiers in neuroscience · 2019Review
- PROneurotrophins and CONSequences.Molecular neurobiology · 2018Review
- Neuroprotective Role of Exogenous Brain-Derived Neurotrophic Factor in Hypoxia-Hypoglycemia-Induced Hippocampal Neuron Injury via Regulating Trkb/MiR134 Signaling.Journal of molecular neuroscience : MN · 2017Article
- ProNGF, but Not NGF, Switches from Neurotrophic to Apoptotic Activity in Response to Reductions in TrkA Receptor Levels.International journal of molecular sciences · 2017Article
- Neurotrophins and B-cell malignancies.Cellular and molecular life sciences : CMLS · 2016Review
- Neurotrophins and Neuropathic Pain: Role in Pathobiology.Molecules (Basel, Switzerland) · 2015Review
- Antiallodynic effects of alpha lipoic acid in an optimized RR-EAE mouse model of MS-neuropathic pain are accompanied by attenuation of upregulated BDNF-TrkB-ERK signaling in the dorsal horn of the spinal cord.Pharmacology research & perspectives · 2015Article
- The role of rab proteins in neuronal cells and in the trafficking of neurotrophin receptors.Membranes · 2014Review
- Pro-neurotrophins, sortilin, and nociception.The European journal of neuroscience · 2014Review
- ProNGF promotes neurite growth from a subset of NGF-dependent neurons by a p75NTR-dependent mechanism.Development (Cambridge, England) · 2013Article
- A single Aplysia neurotrophin mediates synaptic facilitation via differentially processed isoforms.Cell reports · 2013Article
- The neuroprotective roles of BDNF in hypoxic ischemic brain injury.Biomedical reports · 2013Review
- Neurotrophic actions initiated by proNGF in adult sensory neurons may require peri-somatic glia to drive local cleavage to NGF.Journal of neurochemistry · 2012Article
- Pro-nerve growth factor induces autocrine stimulation of breast cancer cell invasion through tropomyosin-related kinase A (TrkA) and sortilin protein.The Journal of biological chemistry · 2012Article
- Electroporation-mediated gene delivery of cleavage-resistant pro-nerve growth factor causes retinal neuro- and vascular degeneration.Molecular vision · 2012Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
The uncleaved, pro-form of nerve growth factor (proNGF) functions as a pro-apoptotic ligand for the p75 neurotrophin receptor (p75NTR). However, some reports have indicated that proneurotrophins bind and activate Trk receptors. In this study, we have examined proneurotrophin receptor binding and activation properties in an attempt to reconcile these findings. We show that proNGF readily binds p75NTR expressed in HEK293T cells but does not interact with TrkA expressed under similar circumstances. Importantly, proNGF activates TrkA tyrosine phosphorylation, induces Erk and Akt activation, and causes PC12 cell differentiation. We show that inhibiting endocytosis or furin activity reduced TrkA activation induced by proNGF but not that induced by mature NGF and that proNGF123, a mutant form of NGF lacking dibasic cleavage sites in the prodomain, does not induce TrkA phosphorylation in PC12 cells. Therefore, endocytosis and cleavage appear to be prerequisites for proNGF-induced TrkA activity. We also found that proBDNF induces activation of TrkB in cerebellar granule neurons and that proBDNF cleavage by furin and metalloproteases facilitates this effect. Taken together, these data indicate that under physiological conditions, proneurotrophins do not directly bind or activate Trk receptors. However, endocytosis and cleavage of proneurotrophins produce processed forms of neurotrophins that are capable of inducing Trk activation.
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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.