ArticleMolecular and cellular biology2013
Interaction of PDK1 with phosphoinositides is essential for neuronal differentiation but dispensable for neuronal survival.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Suicide risk genes impact evolutionarily conserved survival strategies.Translational psychiatry · 2026Article
- Suicide risk genes impact evolutionarily conserved survival strategies.Research square · 2025Article
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein.Science signaling · 2023Article
- Article
- Reducing PDK1/Akt Activity: An Effective Therapeutic Target in the Treatment of Alzheimer's Disease.Cells · 2022Review
- Cannabidiol Enhances Microglial Beta-Amyloid Peptide Phagocytosis and Clearance via Vanilloid Family Type 2 Channel Activation.International journal of molecular sciences · 2022Article
- Article
- Neuronostatin Promotion Soluble Aβ1-42 Oligomers: Induced Dysfunctional Brain Glucose Metabolism in Mice.Neurochemical research · 2020Article
- PDK1 Regulates the Maintenance of Cell Body and the Development of Dendrites of Purkinje Cells by pS6 and PKCγ.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- The Impact of the PI3K/Akt Signaling Pathway in Anxiety and Working Memory in Young and Middle-Aged PDK1 K465E Knock-In Mice.Frontiers in behavioral neuroscience · 2020Article
- Yokukansan, a Kampo medicine, enhances the level of neuronal lineage markers in differentiated P19 embryonic carcinoma cells.Heliyon · 2019Article
- Metabolites and Lipids Associated with Fetal Swine Anatomy via Desorption Electrospray Ionization - Mass Spectrometry Imaging.Scientific reports · 2019Article
- A new microdeletion syndrome involving TBC1D24, ATP6V0C, and PDPK1 causes epilepsy, microcephaly, and developmental delay.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Farnesylation-defective Rheb Increases Axonal Length Independently of mTORC1 Activity in Embryonic Primary Neurons.Experimental neurobiology · 2019Article
- A novel neurotherapeutic for multiple sclerosis, ischemic injury, methamphetamine addiction, and traumatic brain injury.Journal of neuroinflammation · 2019Review
- PAR3-PAR6-atypical PKC polarity complex proteins in neuronal polarization.Cellular and molecular life sciences : CMLS · 2018Review
- PDK1 governs thromboxane generation and thrombosis in platelets by regulating activation of Raf1 in the MAPK pathway.Journal of thrombosis and haemostasis : JTH · 2018Article
- Geometric Navigation of Axons in a Cerebral Pathway: Comparing dMRI with Tract Tracing and Immunohistochemistry.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- Targeting PDK1 for Chemosensitization of Cancer Cells.Cancers · 2017Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
3-Phosphoinositide-dependent protein kinase 1 (PDK1) operates in cells in response to phosphoinositide 3-kinase activation and phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] production by activating a number of AGC kinases, including protein kinase B (PKB)/Akt. Both PDK1 and PKB contain pleckstrin homology (PH) domains that interact with the PtdIns(3,4,5)P(3) second messenger. Disrupting the interaction of the PDK1 PH domain with phosphoinositides by expressing the PDK1 K465E knock-in mutation resulted in mice with reduced PKB activation. We explored the physiological consequences of this biochemical lesion in the central nervous system. The PDK1 knock-in mice displayed a reduced brain size due to a reduction in neuronal cell size rather than cell number. Reduced BDNF-induced phosphorylation of PKB at Thr308, the PDK1 site, was observed in the mutant neurons, which was not rate limiting for the phosphorylation of those PKB substrates governing neuronal survival and apoptosis, such as FOXO1 or glycogen synthase kinase 3 (GSK3). Accordingly, the integrity of the PDK1 PH domain was not essential to support the survival of different embryonic neuronal populations analyzed. In contrast, PKB-mediated phosphorylation of PRAS40 and TSC2, allowing optimal mTORC1 activation and brain-specific kinase (BRSK) protein synthesis, was markedly reduced in the mutant mice, leading to impaired neuronal growth and differentiation.
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