ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Requirement of 3-phosphoinositide-dependent protein kinase-1 for BDNF-mediated neuronal survival.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- BDNF/proBDNF Interplay in the Mediation of Neuronal Apoptotic Mechanisms in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Review
- Knockdown and inhibition of hippocampal GPR17 attenuates lipopolysaccharide-induced cognitive impairment in mice.Journal of neuroinflammation · 2023Article
- Changes in Hippocampal Plasticity in Depression and Therapeutic Approaches Influencing These Changes.Neural plasticity · 2020Review
- A novel neurotherapeutic for multiple sclerosis, ischemic injury, methamphetamine addiction, and traumatic brain injury.Journal of neuroinflammation · 2019Review
- Crosstalk of cell polarity signaling pathways.Protoplasma · 2017Review
- Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development.Frontiers in cellular neuroscience · 2017Article
- Mutation of the 3-Phosphoinositide-Dependent Protein Kinase 1 (PDK1) Substrate-Docking Site in the Developing Brain Causes Microcephaly with Abnormal Brain Morphogenesis Independently of Akt, Leading to Impaired Cognition and Disruptive Behaviors.Molecular and cellular biology · 2016Article
- Galactose-1 phosphate uridylyltransferase (GalT) gene: A novel positive regulator of the PI3K/Akt signaling pathway in mouse fibroblasts.Biochemical and biophysical research communications · 2016Article
- N-docosahexaenoylethanolamine regulates Hedgehog signaling and promotes growth of cortical axons.Biology open · 2015Article
- HLA-DRα1-mMOG-35-55 treatment of experimental autoimmune encephalomyelitis reduces CNS inflammation, enhances M2 macrophage frequency, and promotes neuroprotection.Journal of neuroinflammation · 2015Article
- BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated production of apurinic/apyrimidinic endonuclease 1.Neuromolecular medicine · 2014Article
- Interaction of PDK1 with phosphoinositides is essential for neuronal differentiation but dispensable for neuronal survival.Molecular and cellular biology · 2013Article
- Inhibition of E2F1/CDK1 pathway attenuates neuronal apoptosis in vitro and confers neuroprotection after spinal cord injury in vivo.PloS one · 2012Article
- Increased 90-kDa ribosomal S6 kinase (Rsk) activity is protective against mutant huntingtin toxicity.Molecular neurodegeneration · 2011Article
- Ras family small GTPase-mediated neuroprotective signaling in stroke.Central nervous system agents in medicinal chemistry · 2011Review
- Early gene expression changes in the retinal ganglion cell layer of a rat glaucoma model.Investigative ophthalmology & visual science · 2011Article
- A humanin derivative reduces amyloid beta accumulation and ameliorates memory deficit in triple transgenic mice.PloS one · 2011Article
- Article
- Interstitial flow induces MMP-1 expression and vascular SMC migration in collagen I gels via an ERK1/2-dependent and c-Jun-mediated mechanism.American journal of physiology. Heart and circulatory physiology · 2010Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Although PDK1 regulates several signaling pathways that respond to neurotrophins, direct evidence for its involvement in neurotrophin-mediated survival has not yet been reported. Here we show high neuronal expression of active PDK1 in the rat cortex and hippocampus at the developmental stages with pronounced dependence on extracellular survival signals. Also, in cultured cortical neurons from newborn rats, BDNF resulted in PDK1- and extracellular signal-regulated kinase-1/2 (ERK1/2)-mediated activation of their direct target, the p90 ribosomal S6 kinase 1/2 (RSK1/2). In trophic-deprived cortical neurons, knockdown of endogenous PDK1 attenuated the antiapoptotic survival response to 10 ng/ml BDNF, whereas an overexpressed active mutant form of PDK1 reduced apoptosis. The neuroprotection by BDNF or active PDK1 required RSK1/2. Conversely, PDK1 knockdown reversed the survival effects of combining the overexpressed RSK1 with a low, subprotective BDNF concentration of 2 ng/ml. Likewise, the protection by the overexpressed, active PDK1 was enhanced by coexpression of an active RSK1 mutant. Consistent with the observations that in BDNF-stimulated neurons RSK1/2 activation required both PDK1 and ERK1/2, ERK1/2 knockdown removed BDNF-mediated survival. Selective activation of ERK1/2 with an overexpressed active mutant form of MKK1 resulted in RSK1/2- and PDK1-dependent neuroprotection. Finally, at subprotective plasmid DNA dosage, overexpression of the active MKK1 and PDK1 mutants produced synergistic effect on survival. Our findings indicate a critical role for PDK1-RSK1/2 signaling in BDNF-mediated neuronal survival. Thus, the PDK1 is indispensable for the antiapoptotic effects of the ERK1/2 pathway offering previously unrecognized layer of survival signal processing and integration.
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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.