ArticleMolecular and cellular biology1999
Protein kinase Cdelta mediates neurogenic but not mitogenic activation of mitogen-activated protein kinase in neuronal cells.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 173 citations in OpenAlex.
- Central role of protein kinase Cepsilon in constitutive activation of ERK1/2 and Rac1 in the malignant cells of hairy cell leukemia.The American journal of pathology · 2007Trial
- Mesenchymal Stem Cells Expressing Baculovirus-Engineered Brain-Derived Neurotrophic Factor Improve Peripheral Nerve Regeneration in a Rat Model.Tissue engineering and regenerative medicine · 2025Article
- A, B, C's of Trk Receptors and Their Ligands in Ocular Repair.International journal of molecular sciences · 2022Review
- Brain-Derived Neurotropic Factor in Neurodegenerative Disorders.Biomedicines · 2022Review
- Carotenoids from Marine Sources as a New Approach in Neuroplasticity Enhancement.International journal of molecular sciences · 2022Review
- Flavonoids as a Natural Enhancer of Neuroplasticity-An Overview of the Mechanism of Neurorestorative Action.Antioxidants (Basel, Switzerland) · 2020Review
- NOX2-Dependent Reactive Oxygen Species Regulate Formyl-Peptide Receptor 1-Mediated TrkA Transactivation in SH-SY5Y Cells.Oxidative medicine and cellular longevity · 2019Article
- Engineered BDNF producing cells as a potential treatment for neurologic disease.Expert opinion on biological therapy · 2016Review
- Brain-derived neurotrophic factor and its clinical implications.Archives of medical science : AMS · 2015Article
- Protein kinase Cδ mediates histamine-evoked itch and responses in pruriceptors.Molecular pain · 2015Article
- Molecular and genetic basis of depression.Journal of genetics · 2014Review
- Phosphorylation of serine 779 in fibroblast growth factor receptor 1 and 2 by protein kinase C(epsilon) regulates Ras/mitogen-activated protein kinase signaling and neuronal differentiation.The Journal of biological chemistry · 2013Article
- Article
- Daidzein induces neuritogenesis in DRG neuronal cultures.Journal of biomedical science · 2012Article
- An overview of brain-derived neurotrophic factor and implications for excitotoxic vulnerability in the hippocampus.International journal of peptides · 2011Article
- Role of BDNF and GDNF in drug reward and relapse: a review.Neuroscience and biobehavioral reviews · 2010Review
- Neurotrophins induce neuregulin release through protein kinase Cdelta activation.The Journal of biological chemistry · 2009Article
- Cardiovascular actions of neurotrophins.Physiological reviews · 2009Review
- Protein kinase C subtypes and retinal ischemic preconditioning.Experimental eye research · 2008Article
- Regulation of MAPKs by growth factors and receptor tyrosine kinases.Biochimica et biophysica acta · 2007Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
In several neuronal cell systems, fibroblast-derived growth factor (FGF) and nerve growth factor (NGF) act as neurogenic agents, whereas epidermal growth factor (EGF) acts as a mitogen. The mechanisms responsible for these different cellular fates are unclear. We report here that although FGF, NGF, and EGF all activate mitogen-activated protein (MAP) kinase (extracellular signal-related kinase [ERK]) in rat hippocampal (H19-7) and pheochromocytoma (PC12) cells, the activation of ERK by the neurogenic agents FGF and NGF is dependent upon protein kinase Cdelta (PKCdelta), whereas ERK activation in response to the mitogenic EGF is independent of PKCdelta. Antisense PKCdelta oligonucleotides or the PKCdelta-specific inhibitor rottlerin inhibited FGF- and NGF-induced, but not EGF-induced, ERK activation. In contrast, EGF-induced ERK activation was inhibited by the phosphatidylinositol-3-kinase inhibitor wortmannin, which had no effect upon FGF-induced ERK activation. Rottlerin also inhibited the activation of MAP kinase kinase (MEK) in response to activated Raf, but had no effect upon c-Raf activity or ERK activation by activated MEK. These results indicate that PKCdelta functions either downstream from or in parallel with c-Raf, but upstream of MEK. Inhibition of PKCdelta also blocked neurite outgrowth induced by FGF and NGF in PC12 cells and by activated Raf in H19-7 cells, indicating a role for PKCdelta in the neurogenic effects of FGF, NGF, and Raf. Interestingly, the PKCdelta requirement is apparently cell type specific, since FGF-induced ERK activation was independent of PKCdelta in NIH 3T3 murine fibroblasts, in which FGF is a mitogen. These data demonstrate that PKCdelta contributes to growth factor specificity and response in neuronal cells and may also promote cell-type-specific differences in growth factor signaling.
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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.