ArticleThe Journal of biological chemistry2010
Cannabinoid 1 receptor and interleukin-6 receptor together induce integration of protein kinase and transcription factor signaling to trigger neurite outgrowth.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- Review
- Interleukin-6 serves as a critical factor in various cancer progression and therapy.Medical oncology (Northwood, London, England) · 2024Review
- Neuron-specific RNA-sequencing reveals different responses in peripheral neurons after nerve injury.eLife · 2024Article
- GPR137 Inhibits Cell Proliferation and Promotes Neuronal Differentiation in the Neuro2a Cells.Neurochemical research · 2023Article
- A spatially specified systems pharmacology therapy for axonal recovery after injury.Frontiers in pharmacology · 2023Article
- STAT3 in the dorsal raphe gates behavioural reactivity and regulates gene networks associated with psychopathology.Molecular psychiatry · 2021Article
- Cannabinoid Signaling in Auditory Function and Development.Frontiers in molecular neuroscience · 2021Article
- Article
- CBFrontiers in cellular neuroscience · 2020Article
- Microglia priming by interleukin-6 signaling is enhanced in aged mice.Journal of neuroimmunology · 2018Article
- CBAdvances in pharmacology (San Diego, Calif.) · 2017Review
- Looking downstream: the role of cyclic AMP-regulated genes in axonal regeneration.Frontiers in molecular neuroscience · 2015Review
- Neuroglobin promotes neurite outgrowth via differential binding to PTEN and Akt.Molecular neurobiology · 2014Article
- Diabetes impairs an interleukin-1β-dependent pathway that enhances neurite outgrowth through JAK/STAT3 modulation of mitochondrial bioenergetics in adult sensory neurons.Molecular brain · 2013Article
- Early methyl donor deficiency may induce persistent brain defects by reducing Stat3 signaling targeted by miR-124.Cell death & disease · 2013Article
- Endocannabinoid metabolism in the prefrontal cortex in schizophrenia.Schizophrenia research · 2013Article
- Endocannabinoids via CB₁ receptors act as neurogenic niche cues during cortical development.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2012Review
- Brain indoleamine 2,3-dioxygenase contributes to the comorbidity of pain and depression.The Journal of clinical investigation · 2012Article
- Hierarchical clustering of gene expression patterns in the Eomes + lineage of excitatory neurons during early neocortical development.BMC neuroscience · 2012Article
- Endocannabinoids stimulate human melanogenesis via type-1 cannabinoid receptor.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Activation of the G(o/i)-coupled cannabinoid 1 receptor (CB1R) has been shown to induce neurite outgrowth in Neuro2A cells through activation of Src kinase and STAT3 transcription factor. Signaling by the interleukin 6 receptor (IL-6R) also activates STAT3 through Jak kinase. We studied if signals from the two pathways could be integrated in a synergistic manner to trigger neurite outgrowth in Neuro2A cells. At low concentrations, when agonist at either receptor by itself has no effect, we found that CB1R and IL-6R stimulation together induced synergistic neurite outgrowth. Signal integration requires activation of transcription factors by Src, Jak, and mitogen-activated protein kinases. Mitogen-activated protein kinase can be activated by both receptors and shows enhanced early activation in the presence of both ligands. CREB and STAT3 transcription factors are required for synergy and show enhanced DNA-binding activity when both receptors are activated. STAT3 plays a critical role in integration of the signals downstream of the two receptors. When both pathways are activated, STAT3 phosphorylation is sustained for 6 h. This prolonged activation of STAT3 requires deactivation of SHP2 phosphatase. Reduction of SHP2 levels by RNA interference results in greater synergy in neurite outgrowth. Simultaneous knockdown of both SHP2 and STAT3 blocks the synergistic triggering of neurite outgrowth, indicating that STAT3 is downstream of SHP2. CB1R and IL-6R co-stimulation enhanced the differentiation of rat cortical neuron primary cultures. These results provide a mechanism where multiple protein kinases and transcription factors interact to integrate signals from G protein-coupled and cytokine receptor to evoke neurite outgrowth in Neuro2A 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.