ArticleMolecular and cellular biology2008
Mutation of the PDK1 PH domain inhibits protein kinase B/Akt, leading to small size and insulin resistance.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 129 citations in OpenAlex.
- Rare Variants of Immune-Related Genes Increase Susceptibility to Autoimmune Encephalitis: An Association Study.Neurology international · 2025Article
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- 3-Phosphoinositide-Dependent Kinase 1 as a Therapeutic Target for Treating Diabetes.Current diabetes reviews · 2025Review
- Diet induced insulin resistance is due to induction of PTEN expression.Research square · 2024Article
- Chaperone-mediated autophagy as a modulator of aging and longevity.Frontiers in aging · 2024Review
- PTEN is both an activator and a substrate of chaperone-mediated autophagy.The Journal of cell biology · 2023Article
- 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
- Activation of the essential kinase PDK1 by phosphoinositide-driven trans-autophosphorylation.Nature communications · 2022Article
- The Genetics of Diabetes: What We Can Learn fromInternational journal of molecular sciences · 2021Review
- Phosphorylation of Akt at Thr308 regulates p-eNOS Ser1177 during physiological conditions.FEBS open bio · 2021Article
- Article
- PDK1 Is Required for Maintenance of CD4Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- 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
- Article
- 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
- The 3-Phosphoinositide-Dependent Protein Kinase 1 Inhibits Rod Photoreceptor Development.Frontiers in cell and developmental biology · 2018Article
- Review
- Transcriptomics, metabolomics and histology indicate that high-carbohydrate diet negatively affects the liver health of blunt snout bream (Megalobrama amblycephala).BMC genomics · 2017Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
PDK1 activates a group of kinases, including protein kinase B (PKB)/Akt, p70 ribosomal S6 kinase (S6K), and serum and glucocorticoid-induced protein kinase (SGK), that mediate many of the effects of insulin as well as other agonists. PDK1 interacts with phosphoinositides through a pleckstrin homology (PH) domain. To study the role of this interaction, we generated knock-in mice expressing a mutant of PDK1 incapable of binding phosphoinositides. The knock-in mice are significantly small, insulin resistant, and hyperinsulinemic. Activation of PKB is markedly reduced in knock-in mice as a result of lower phosphorylation of PKB at Thr308, the residue phosphorylated by PDK1. This results in the inhibition of the downstream mTOR complex 1 and S6K1 signaling pathways. In contrast, activation of SGK1 or p90 ribosomal S6 kinase or stimulation of S6K1 induced by feeding is unaffected by the PDK1 PH domain mutation. These observations establish the importance of the PDK1-phosphoinositide interaction in enabling PKB to be efficiently activated with an animal model. Our findings reveal how reduced activation of PKB isoforms impinges on downstream signaling pathways, causing diminution of size as well as insulin resistance.
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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.