PDK1

Summary

Gene Symbol: PDK1
Description: pyruvate dehydrogenase kinase 1
Alias: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial, pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial, PDH kinase 1, mitochondrial pyruvate dehydrogenase, lipoamide, kinase isoenzyme 1, pyruvate dehydrogenase kinase, isoenzyme 1
Species: human
Products:     PDK1

Top Publications

  1. Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, et al. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell. 2002;110:177-89 pubmed
    ..elegans raptor yields an array of phenotypes that closely resemble those produced by inactivation of Ce-TOR. Thus, raptor is an essential scaffold for the mTOR-catalyzed phosphorylation of 4EBP1 and mediates TOR action in vivo. ..
  2. Sugden M, Holness M. Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs. Am J Physiol Endocrinol Metab. 2003;284:E855-62 pubmed
  3. Kim J, Tchernyshyov I, Semenza G, Dang C. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3:177-85 pubmed
    ..the tricarboxylic acid cycle (TCA) by directly trans-activating the gene encoding pyruvate dehydrogenase kinase 1 (PDK1). PDK1 inactivates the TCA cycle enzyme, pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA...
  4. Lu Z, Cox Hipkin M, Windsor W, Boyapati A. 3-phosphoinositide-dependent protein kinase-1 regulates proliferation and survival of cancer cells with an activated mitogen-activated protein kinase pathway. Mol Cancer Res. 2010;8:421-32 pubmed publisher
    ..This second messenger leads to the recruitment of 3-phosphoinositide-dependent protein kinase-1 (PDK1) to the proximal side of the plasma membrane, which results in the activation of AKT kinase...
  5. Ding Z, Liang J, Li J, Lu Y, Ariyaratna V, Lu Z, et al. Physical association of PDK1 with AKT1 is sufficient for pathway activation independent of membrane localization and phosphatidylinositol 3 kinase. PLoS ONE. 2010;5:e9910 pubmed publisher
    ..phosphate-mediated recruitment of AKT and its upstream kinases, including 3-Phosphoinositide-dependent kinase 1 (PDK1), to the inner surface of the cell membrane...
  6. Gagliardi P, di Blasio L, Orso F, Seano G, Sessa R, Taverna D, et al. 3-phosphoinositide-dependent kinase 1 controls breast tumor growth in a kinase-dependent but Akt-independent manner. Neoplasia. 2012;14:719-31 pubmed
    3-phosphoinositide-dependent protein kinase 1 (PDK1) is the pivotal element of the phosphatidylinositol 3 kinase (PI3K) signaling pathway because it phosphorylates Akt/PKB through interactions with phosphatidylinositol 3,4,5 phosphate...
  7. Tian X, Rusanescu G, Hou W, Schaffhausen B, Feig L. PDK1 mediates growth factor-induced Ral-GEF activation by a kinase-independent mechanism. EMBO J. 2002;21:1327-38 pubmed
    ..Here we show that Ral-GEF stimulation by EGF involves an additional mechanism, PI3-K-dependent kinase 1 (PDK1)-induced enhancement of Ral-GEF catalytic activity...
  8. Pinner S, Sahai E. PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE. Nat Cell Biol. 2008;10:127-37 pubmed publisher
    ..In this study, we show that PDK1 is required for phosphorylation of myosin light chain and cell motility, both on deformable gels and in vivo...
  9. Shen X, Xi G, Radhakrishnan Y, Clemmons D. PDK1 recruitment to the SHPS-1 signaling complex enhances insulin-like growth factor-i-stimulated AKT activation and vascular smooth muscle cell survival. J Biol Chem. 2010;285:29416-24 pubmed publisher
    ..Therefore, we investigated the mechanism of PDK1 recruitment to the SHPS-1 signaling complex and the consequences of disrupting PDK1 recruitment for downstream ..

More Information

Publications127 found, 100 shown here

  1. Lin C, Lee H, Lee M, Pan S, Ke C, Chiu A, et al. Role of Mitochondrial DNA Copy Number Alteration in Human Renal Cell Carcinoma. Int J Mol Sci. 2016;17: pubmed publisher
    ..subunit A (LDHA); and hypoxia-inducible factors the HIF-1? and HIF-2?, pyruvate dehydrogenase kinase 1 (PDK1), and pyruvate dehydrogenase E1 component ? subunit (PDHA1) were analyzed by Western blot or Q-PCR...
  2. Lang F, Stournaras C. Serum and glucocorticoid inducible kinase, metabolic syndrome, inflammation, and tumor growth. Hormones (Athens). 2013;12:160-71 pubmed
    ..is activated by insulin and growth factors via phosphatidylinositol-3-kinase, 3-phosphoinositide dependent-kinase PDK1, and mTOR. SGK1 up-regulates the Na⁺/K⁺-ATPase, a variety of carriers (e.g...
  3. Cotroneo E, Ashek A, Wang L, Wharton J, Dubois O, Bozorgi S, et al. Iron homeostasis and pulmonary hypertension: iron deficiency leads to pulmonary vascular remodeling in the rat. Circ Res. 2015;116:1680-90 pubmed publisher
    ..Along with upregulation of the glucose transporter, glucose transporter 1, and glycolytic genes, hk1 and pdk1, lung fluorine-18-labeled 2-fluoro-2-deoxyglucose ligand uptake was significantly increased in IDD rats...
  4. Vallée A, Lecarpentier Y, Guillevin R, Vallee J. Thermodynamics in Neurodegenerative Diseases: Interplay Between Canonical WNT/Beta-Catenin Pathway-PPAR Gamma, Energy Metabolism and Circadian Rhythms. Neuromolecular Med. 2018;20:174-204 pubmed publisher
    ..activated enzymes, such as glucose transporter (Glut), pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK1), monocarboxylate lactate transporter 1 (MCT-1), lactic dehydrogenase kinase-A (LDH-A) and inactivation of pyruvate ..
  5. Wiedenhoft H, Hayashi L, Coffin A. PI3K and Inhibitor of Apoptosis Proteins Modulate Gentamicin- Induced Hair Cell Death in the Zebrafish Lateral Line. Front Cell Neurosci. 2017;11:326 pubmed publisher
    ..Our bioinformatics analysis identified the pro-survival proteins phosphoinositide-dependent kinase-1 (PDK1) and X-linked inhibitor of apoptosis protein (Xiap) as potential mediators of gentamicin-induced hair cell damage...
  6. Kan J, Velliquette R, Grann K, Burns C, Scholten J, Tian F, et al. A novel botanical formula prevents diabetes by improving insulin resistance. BMC Complement Altern Med. 2017;17:352 pubmed publisher
    ..The reduction in epididymal adipose tissue GLUT4 and PDK1 expression induced by high fat diet and alloxan was blunted by the botanical test formula...
  7. Chattopadhyay T, Singh R, Gupta S, Surolia A. Bone morphogenetic protein-7 (BMP-7) augments insulin sensitivity in mice with type II diabetes mellitus by potentiating PI3K/AKT pathway. Biofactors. 2017;43:195-209 pubmed publisher
    ..and muscle by increasing Glut4 translocation to the plasma membrane through phosphorylation and activation of PDK1 and Akt, and phosphorylation and translocation of FoxO1 to the cytoplasm in liver/HepG2 cells...
  8. Liu Y, Li X, Xie C, Luo X, Bao Y, Wu B, et al. Prevention Effects and Possible Molecular Mechanism of Mulberry Leaf Extract and its Formulation on Rats with Insulin-Insensitivity. PLoS ONE. 2016;11:e0152728 pubmed publisher
    ..The changes of JNK, IRS1, and PDK1 were confirmed by western blot analysis...
  9. Gao B, Sun W, Meng X, Xue D, Zhang W. Screening of differentially expressed protein kinases in bone marrow endothelial cells and the protective effects of the p38a inhibitor SB203580 on bone marrow in liver fibrosis. Mol Med Rep. 2016;14:4629-4637 pubmed publisher
    ..kinase genes in human bone marrow endothelial cells in LC from the microarray data, including p38a, AKT1 and PDK1. Pathway analysis revealed that these kinase genes were enriched in certain important LC?associated pathways (e.g...
  10. Sonoda Y, Tooyama I, Mukai H, Maeda K, Akiyama H, Kawamata T. S6 kinase phosphorylated at T229 is involved in tau and actin pathologies in Alzheimer's disease. Neuropathology. 2016;36:325-32 pubmed publisher
    ..there is little information available about S6K proteins directly phosphorylated at T229 (pT229-S6K) by the PI3K-PDK1 pathway...
  11. Yu Z, Cai M, Xiang J, Zhang Z, Zhang J, Song X, et al. PI3K/Akt pathway contributes to neuroprotective effect of Tongxinluo against focal cerebral ischemia and reperfusion injury in rats. J Ethnopharmacol. 2016;181:8-19 pubmed publisher
    ..We also found that TXL up-regulated the expression levels of p-PDK1, p-Akt, p-c-Raf, p-BAD and down-regulated Cleaved caspase 3 expression notably, which were partially reversed by ..
  12. Vasu S, Ojo O, Moffett R, Conlon J, Flatt P, Abdel Wahab Y. Anti-diabetic actions of esculentin-2CHa(1-30) and its stable analogues in a diet-induced model of obesity-diabetes. Amino Acids. 2017;49:1705-1717 pubmed publisher
    ..on expression of islet genes (Ins1, Slc2a2, Pdx1) and skeletal muscle genes involved in insulin action (Slc2a4, Pdk1, Irs1, Akt1)...
  13. Shen J, Tsoi H, Liang Q, Chu E, Liu D, Yu A, et al. Oncogenic mutations and dysregulated pathways in obesity-associated hepatocellular carcinoma. Oncogene. 2016;35:6271-6280 pubmed publisher
    ..MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/3-phosphoinositide-dependent protein kinase-1 (PDK1)/Akt pathways. In conclusion, we have identified mutation signature and pathways in NAFLD-associated HCC...
  14. Wang T, Chen H, Lv K, Ji G, Liang F, Zhang Y, et al. Activation of HIF-1? and its downstream targets in rat hippocampus after long-term simulated microgravity exposure. Biochem Biophys Res Commun. 2017;485:591-597 pubmed publisher
    ..The expression of pyruvate dehydrogenase kinase 1 (PDK1), lactate dehydrogenase A (LDHA) and vascular endothelial growth factor (VEGF), three well-defined downstream ..
  15. Khan A, Allende Vega N, Gitenay D, Gerbal Chaloin S, Gondeau C, Vo D, et al. The PDK1 Inhibitor Dichloroacetate Controls Cholesterol Homeostasis Through the ERK5/MEF2 Pathway. Sci Rep. 2017;7:10654 pubmed publisher
    ..In summary, our results indicate that DCA, by inducing OXPHOS, promotes ERK5/MEF2 activation leading to LDLR expression. The ERK5/MEF2 pathway offers an interesting pharmacological target for drug development. ..
  16. Haugrud A, Zhuang Y, Coppock J, Miskimins W. Dichloroacetate enhances apoptotic cell death via oxidative damage and attenuates lactate production in metformin-treated breast cancer cells. Breast Cancer Res Treat. 2014;147:539-50 pubmed publisher
    ..Metformin-induced oxidative damage is enhanced by DCA through PDK1 inhibition which also diminishes metformin promoted lactate production...
  17. Zhang D, Bae C, Lee J, Lee J, Jin Z, Kang M, et al. The bone anabolic effects of irisin are through preferential stimulation of aerobic glycolysis. Bone. 2018;114:150-160 pubmed publisher
    ..abundance of representative enzymes such as lactate dehydrogenase A (LDHA) and pyruvate dehydrogenase kinase 1 (PDK1), together with increased lactate levels...
  18. Lang F, Huang D, Vallon V. SGK, renal function and hypertension. J Nephrol. 2010;23 Suppl 16:S124-9 pubmed
    ..by insulin and growth factors via phosphatidylinositol-3-kinase and the 3-phosphoinositide-dependent kinase PDK1. SGK1 enhances the activity of a variety of ion channels such as ENaC, TRPV5, ROMK, KCNE1/KCNQ1 and ClCKb; carriers ..
  19. Zhang X, Liu Z, Xiao Q, Zeng C, Lai C, Fan X, et al. Donor Treatment With a Hypoxia-Inducible Factor-1 Agonist Prevents Donation After Cardiac Death Liver Graft Injury in a Rat Isolated Perfusion Model. Artif Organs. 2018;42:280-289 pubmed publisher
    ..The beneficial effects of FG-4592 is attributed in part to the accumulation of HIF-1 and ultimately increased PDK1 production...
  20. Shen H, Hau E, Joshi S, Dilda P, McDonald K. Sensitization of Glioblastoma Cells to Irradiation by Modulating the Glucose Metabolism. Mol Cancer Ther. 2015;14:1794-804 pubmed publisher
    ..together with upregulated hypoxia-inducible factor (HIF)-1α and its target pyruvate dehydrogenase kinase 1 (PDK1)...
  21. Lerat H, Imache M, Polyte J, Gaudin A, Mercey M, Donati F, et al. Hepatitis C virus induces a prediabetic state by directly impairing hepatic glucose metabolism in mice. J Biol Chem. 2017;292:12860-12873 pubmed publisher
    ..Early steps of the hepatic insulin signaling pathway, from IRS2 to PDK1 phosphorylation, were constitutively impaired in FL-N/35 primary hepatocytes via deregulation of TNF?/SOCS3...
  22. Vallée A, Lecarpentier Y, Guillevin R, Vallée J. Aerobic Glycolysis Hypothesis Through WNT/Beta-Catenin Pathway in Exudative Age-Related Macular Degeneration. J Mol Neurosci. 2017;62:368-379 pubmed publisher
    ..then HIF-1alpha which activates glycolytic enzymes: glucose transporter (Glut), pyruvate dehydrogenase kinase 1 (PDK1), lactate dehydrogenase A (LDH-A), and monocarboxylate lactate transporter (MCT-1)...
  23. Chen P, Cheng C, Shih C, Ho K, Lin C, Lee C, et al. The Inhibition of microRNA-128 on IGF-1-Activating mTOR Signaling Involves in Temozolomide-Induced Glioma Cell Apoptotic Death. PLoS ONE. 2016;11:e0167096 pubmed publisher
    ..including mTOR, rapamycin-insensitive companion of mTOR, insulin-like growth factor 1, and PIK3R1, but not PDK1, were direct target genes of miR-128. TMZ inhibited mTOR signaling through miR-128 regulation...
  24. Bai X, Li P, Xie Y, Guo C, Sun Y, Xu Q, et al. Overexpression of 3-phosphoinositide-dependent protein kinase-1 is associated with prognosis of gastric carcinoma. Tumour Biol. 2016;37:2333-9 pubmed publisher
    This study investigated the correlation between the expression of 3-phosphoinositide-dependent protein kinase-1 (PDK1) and the prognosis of gastric carcinoma patients...
  25. Sharma V, Singh A, Srivastava S, Kumar V, Gardi N, Nalwa A, et al. Increased expression of platelet-derived growth factor associated protein-1 is associated with PDGF-B mediated glioma progression. Int J Biochem Cell Biol. 2016;78:194-205 pubmed publisher
    ..expression of PDGF-B and its downstream genes (Akt1/Protein kinase B (PKB) and phosphoinositide-dependent kinase-1 (PDK1) by up to 50%...
  26. Reyer A, Schindler N, Ohde D, Walz C, Kunze M, Tuchscherer A, et al. The RGD sequence present in IGFBP-2 is required for reduced glucose clearance after oral glucose administration in female transgenic mice. Am J Physiol Endocrinol Metab. 2015;309:E409-17 pubmed publisher
    ..Although we do not have reason to assume altered activation of IGF-I receptor or PDK1/Akt activation in both models, we have identified increased levels of integrin-linked kinase and focal adhesion ..
  27. Zaru R, Matthews S, Edgar A, Prescott A, Gomez Nicola D, Hanauer A, et al. The PDK1-Rsk Signaling Pathway Controls Langerhans Cell Proliferation and Patterning. J Immunol. 2015;195:4264-72 pubmed publisher
    ..Our results identify a key signaling pathway needed to establish a normal LC network and suggest that LC might maintain epidermal surveillance by increasing their "footprint" when their numbers are limited. ..
  28. Schulze J, Saladino G, Busschots K, Neimanis S, Süß E, Odadzic D, et al. Bidirectional Allosteric Communication between the ATP-Binding Site and the Regulatory PIF Pocket in PDK1 Protein Kinase. Cell Chem Biol. 2016;23:1193-1205 pubmed publisher
    ..AGC kinases have a conserved allosteric site, the phosphoinositide-dependent protein kinase 1 (PDK1)-interacting fragment (PIF) pocket, which regulates protein ATP-binding, activity, and interaction with substrates...
  29. Rogel A, Willoughby J, Buchan S, Leonard H, Thirdborough S, Al Shamkhani A. Akt signaling is critical for memory CD8+ T-cell development and tumor immune surveillance. Proc Natl Acad Sci U S A. 2017;114:E1178-E1187 pubmed publisher
    ..Using CD8+ T cells from pdk1K465E/K465E knockin mice, we found that decreased Akt activity inhibited the survival of T ..
  30. Alcantara D, Elmslie F, Tetreault M, Bareke E, Hartley T, Majewski J, et al. SHORT syndrome due to a novel de novo mutation in PRKCE (Protein Kinase C?) impairing TORC2-dependent AKT activation. Hum Mol Genet. 2017;26:3713-3721 pubmed publisher
    ..Kinase analysis showed that the variant resulted in a partial loss-of-function. Whilst interaction with PDK1 and the mTORC2 complex component SIN1 was preserved in the mutant PKC?, it bound to SIN1 with a higher affinity ..
  31. Gao X, Harris T. Steady-state kinetic mechanism of PDK1. J Biol Chem. 2006;281:21670-81 pubmed
    b>PDK1 catalyzes phosphorylation of Thr in the conserved activation loop region of a number of its downstream AGC kinase family members...
  32. Hoshi N, Langeberg L, Gould C, Newton A, Scott J. Interaction with AKAP79 modifies the cellular pharmacology of PKC. Mol Cell. 2010;37:541-50 pubmed publisher
    ..suggest that context-dependent protein-protein interactions alter the susceptibility of another protein kinase, PDK1, to ATP analog inhibitors...
  33. Zheng N, Ding X, Sun A, Jahan R. PDK1 Activity Regulates Proliferation, Invasion and Growth of Hemangiomas. Cell Physiol Biochem. 2015;36:1903-10 pubmed publisher
    ..3-phosphoinositide-dependent kinase 1(PDK1), an upstream protein of Akt, regulates the activity of Akt and its downstream kinases...
  34. Vieira G, Chockalingam S, Melegh Z, Greenhough A, Malik S, Szemes M, et al. LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/β-catenin signalling in neuroblastoma. Oncotarget. 2015;6:40053-67 pubmed publisher
    ..Akt signalling is also decreased by a Rictor dependent, PDK1-independent mechanism...
  35. Lim S, Liu H, Madeira da Silva L, Arora R, Liu Z, Phillips J, et al. Immunoregulatory Protein B7-H3 Reprograms Glucose Metabolism in Cancer Cells by ROS-Mediated Stabilization of HIF1?. Cancer Res. 2016;76:2231-42 pubmed publisher
    ..B7-H3 also increased the protein levels of HIF1? and its downstream targets, LDHA and PDK1, key enzymes in the glycolytic pathway...
  36. Gudiksen A, Pilegaard H. PGC-1? and fasting-induced PDH regulation in mouse skeletal muscle. Physiol Rep. 2017;5: pubmed publisher
    ..PGC-1? MKO mice had lower skeletal muscle PDH-E1?, PDK1, 2, 4, and pyruvate dehydrogenase phosphatase (PDP1) protein content than controls, but this did not prevent the ..
  37. Hassanlou M, Soltani B, Mowla S. Expression and Function of hsa-miR-6165 in Human Cell Lines and During the NT2 Cell Neural Differentiation Process. J Mol Neurosci. 2017;63:254-266 pubmed publisher
    ..Furthermore, hsa-miR-6165 overexpression resulted in significant downregulation of ABLIM-1, PVRL1, and PDK1 target genes, while it attenuates NT2 neural differentiation...
  38. Liu Y, Yang K, Sun X, Fang P, Shi H, Xu J, et al. MiR-138 suppresses airway smooth muscle cell proliferation through the PI3K/AKT signaling pathway by targeting PDK1. Exp Lung Res. 2015;41:363-9 pubmed publisher
    ..to determine whether microRNA-138 (miR-138) binds directly to 3-phosphoinositide-dependent protein kinase-1(PDK1) 3' untranslated region (3'-UTR) to alter gene expression...
  39. Kroon E, Schulze J, Süß E, Camacho C, Biondi R, Dömling A. Discovery of a Potent Allosteric Kinase Modulator by Combining Computational and Synthetic Methods. Angew Chem Int Ed Engl. 2015;54:13933-6 pubmed publisher
    The rational design of allosteric kinase modulators is challenging but rewarding. The protein kinase PDK1, which lies at the center of the growth-factor signaling pathway, possesses an allosteric regulatory site previously validated both ..
  40. Gómez Suárez M, Gutiérrez Martínez I, Hernández Trejo J, Hernández Ruiz M, Suárez Pérez D, Candelario A, et al. 14-3-3 Proteins regulate Akt Thr308 phosphorylation in intestinal epithelial cells. Cell Death Differ. 2016;23:1060-72 pubmed publisher
    ..Phosphorylation of Thr308 of Akt by phosphoinositide-dependent kinase 1 (PDK1) is critical for optimal stimulation of its kinase activity...
  41. Xu Y, Wang X, Chen Y, Chen S, Yang X, Sun Y, et al. Integration of Receptor Tyrosine Kinases Determines Sensitivity to PI3K?-selective Inhibitors in Breast Cancer. Theranostics. 2017;7:974-986 pubmed publisher
    ..PI3K-regulated ERK phosphorylation was independent of canonical PDK1/AKT/mTOR pathway, while it was associated with RAF/MEK...
  42. Gagliardi P, Puliafito A, Primo L. PDK1: At the crossroad of cancer signaling pathways. Semin Cancer Biol. 2018;48:27-35 pubmed publisher
    ..An increasing amount of evidence hints at 3-phosphoinositide dependent protein kinase-1 (PDK1 or PDPK1) as an intriguing and underexplored target for cancer therapy...
  43. Huang B, Newcomer K, Kevala K, Barnaeva E, Zheng W, Hu X, et al. Identification of 4-phenylquinolin-2(1H)-one as a specific allosteric inhibitor of Akt. Sci Rep. 2017;7:11673 pubmed publisher
    ..4-Phenylquinolin-2(1H)-one did not alter the activity of upstream kinases including PI3K, PDK1, and mTORC2 as well as closely related kinases that affect cell proliferation and survival such as SGK1, PKA, PKC, ..
  44. Zhang J, Zhu Y, Shi Y, Han Y, Liang C, Feng Z, et al. Fluoride-Induced Autophagy via the Regulation of Phosphorylation of Mammalian Targets of Rapamycin in Mice Leydig Cells. J Agric Food Chem. 2017;65:8966-8976 pubmed publisher
    ..Additionally, fluoride exposure significantly changed the mRNA expression of the PDK1, TSC, and Atg13 regulator genes in primary Leydig cells but not in testicular cells...
  45. Emmanouilidi A, Falasca M. Targeting PDK1 for Chemosensitization of Cancer Cells. Cancers (Basel). 2017;9: pubmed publisher
    ..In this review, we discuss the potential role of PDK1 in the development of chemoresistance in different types of malignancy, and the design and application of potent ..
  46. Wheeler D, Zoncu R, Root D, Sabatini D, Sawyers C. Identification of an oncogenic RAB protein. Science. 2015;350:211-7 pubmed publisher
    ..RAB35 functions downstream of growth factor receptors and upstream of PDK1 and mTORC2 and copurifies with PI3K in immunoprecipitation assays...
  47. Ko M, Yang M, Youn S, Lan C, Tseng T. Intact subepidermal nerve fibers mediate mechanical hypersensitivity via the activation of protein kinase C gamma in spared nerve injury. Mol Pain. 2016;12: pubmed publisher
    ..In phosphoinositide-3 kinase pathway, pyruvate dehydrogenase kinase 1 (PDK1) participates in the regulation of neuronal plasticity for central sensitization...
  48. Hautala L, Koistinen R, Koistinen H. Repressed PKC? activation in glycodelin-expressing cells mediates resistance to phorbol ester and TGF?. Cell Signal. 2016;28:1463-9 pubmed publisher
    ..HEC-1B cells have repressed protein kinase C delta (PKC?) activation, likely due to downregulation of PDK1, and are resistant to phenotypic change and enhanced migration induced by phorbol 12-myristate 13-acetate (PMA)...
  49. Zhang W, Zhang S, Hu X, Tam K. Phenyl butyrate inhibits pyruvate dehydrogenase kinase 1 and contributes to its anti-cancer effect. Eur J Pharm Sci. 2017;110:93-100 pubmed publisher
    ..dehydrogenase (PDH) phosphorylation level and increase PDH activity by inhibiting pyruvate dehydrogenase kinase 1 (PDK1) in fibroblast cells, PDH deficiency zebrafish and wild type mice...
  50. Park J, Leong M, Buse P, Maiyar A, Firestone G, Hemmings B. Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway. EMBO J. 1999;18:3024-33 pubmed
    ..Cotransfection of PDK1 with SGK caused a 6-fold activation of SGK activity, whereas kinase-dead PDK1 caused no activation...
  51. Kim J, Gao P, Liu Y, Semenza G, Dang C. Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol Cell Biol. 2007;27:7381-93 pubmed
  52. Chen S, Liao D, Shen T, Yang H, Chen K, Chen C. Genetic signatures of heroin addiction. Medicine (Baltimore). 2016;95:e4473 pubmed publisher
    ..We first measured the transcript level of 13 genes (RASA1, PRKCB, PDK1, JUN, CEBPG, CD74, CEBPB, AUTS2, ENO2, IMPDH2, HAT1, MBD1, and RGS3) in lymphoblastoid cell lines in a sample of ..
  53. Chae Y, Vaira V, Caino M, Tang H, Seo J, Kossenkov A, et al. Mitochondrial Akt Regulation of Hypoxic Tumor Reprogramming. Cancer Cell. 2016;30:257-272 pubmed publisher
    ..that active Akt accumulates in the mitochondria during hypoxia and phosphorylates pyruvate dehydrogenase kinase 1 (PDK1) on Thr346 to inactivate the pyruvate dehydrogenase complex...
  54. Huang W, Quan C, Duan P, Tang S, Chen W, Yang K. Nonylphenol induced apoptosis and autophagy involving the Akt/mTOR pathway in prepubertal Sprague-Dawley male rats in vivo and in vitro. Toxicology. 2016;373:41-53 pubmed publisher
    ..triggered apoptosis related to oxidative stress, and disturbed mRNA and/or protein levels of PI3K, PTEN, PDK1, p-Akt, p-mTOR, p70S6K, caspase-3, LC3B. NP induced morphological abnormality in epididymal sperm (2.00-, 3...
  55. Dai Z, Pan S, Chen C, Cao L, Li X, Chen X, et al. Down-regulation of succinate dehydrogenase subunit B and up-regulation of pyruvate dehydrogenase kinase 1 predicts poor prognosis in recurrent nasopharyngeal carcinoma. Tumour Biol. 2016;37:5145-52 pubmed publisher
    Succinate dehydrogenase subunit B (SDHB) and pyruvate dehydrogenase kinase 1 (PDK1) play key roles in the regulation of growth and survival of various cancers...
  56. Fan Y, Wang Y, Wang K. Prostaglandin E2 stimulates normal bronchial epithelial cell growth through induction of c-Jun and PDK1, a kinase implicated in oncogenesis. Respir Res. 2015;16:149 pubmed publisher
    ..We evaluated the effects of c-Jun and 3-phosphoinositede dependent protein kinase-1 (PDK1) in mediating epithelial cell hyperplasia induced by PGE2...
  57. Sen T, Sen N. Treatment with an activator of hypoxia-inducible factor 1, DMOG provides neuroprotection after traumatic brain injury. Neuropharmacology. 2016;107:79-88 pubmed publisher
    ..downstream proteins such as Vascular endothelial growth factor (VEGF), Phosphoinositide-dependent kinase-1 and 4 (PDK1, PDK4) and Erythropoietin (EPO)...
  58. Sestito S, Daniele S, Nesi G, Zappelli E, Di Maio D, Marinelli L, et al. Locking PDK1 in DFG-out conformation through 2-oxo-indole containing molecules: Another tools to fight glioblastoma. Eur J Med Chem. 2016;118:47-63 pubmed publisher
    The phosphoinositide-dependent kinase-1 (PDK1) is one of the main components of the PI3K/Akt pathway...
  59. Politz O, Siegel F, Bärfacker L, Bömer U, Hägebarth A, Scott W, et al. BAY 1125976, a selective allosteric AKT1/2 inhibitor, exhibits high efficacy on AKT signaling-dependent tumor growth in mouse models. Int J Cancer. 2017;140:449-459 pubmed publisher
    ..this proposed allosteric binding mode, BAY 1125976 bound to inactive AKT1 and inhibited T308 phosphorylation by PDK1, while the activity of truncated AKT proteins lacking the pleckstrin homology domain was not inhibited...
  60. Iaconelli J, Lalonde J, Watmuff B, Liu B, Mazitschek R, Haggarty S, et al. Lysine Deacetylation by HDAC6 Regulates the Kinase Activity of AKT in Human Neural Progenitor Cells. ACS Chem Biol. 2017;12:2139-2148 pubmed publisher
    ..localization and subsequent activation through phosphorylation by phosphoinositide-dependent protein kinase 1 (PDK1)...
  61. Wang C, Liu M, Riojas R, Xin X, Gao Z, Zeng R, et al. Protein kinase C theta (PKCtheta)-dependent phosphorylation of PDK1 at Ser504 and Ser532 contributes to palmitate-induced insulin resistance. J Biol Chem. 2009;284:2038-44 pubmed publisher
    ..study, we show that palmitate-induced serine phosphorylation of phosphoinositide-dependent protein kinase-1 (PDK1) negatively regulates insulin signaling...
  62. Sundaresan N, Pillai V, Wolfgeher D, Samant S, Vasudevan P, Parekh V, et al. The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy. Sci Signal. 2011;4:ra46 pubmed publisher
    ..PIP(3)), which promotes membrane localization and phosphorylation of Akt by the upstream kinase PDK1 (phosphoinositide-dependent protein kinase 1)...
  63. Qiu X, Wei R, Li Y, Zhu Q, Xiong C, Chen Y, et al. NEDL2 regulates enteric nervous system and kidney development in its Nedd8 ligase activity-dependent manner. Oncotarget. 2016;7:31440-53 pubmed publisher
    ..analysis indicated that NEDL2 appears to act like a scaffold protein to recruit SHC, Grb2, PI3K (p110 and p85), PDK1 and Akt together to promote the signaling transduction...
  64. Dupuy F, Tabariès S, Andrzejewski S, Dong Z, Blagih J, Annis M, et al. PDK1-Dependent Metabolic Reprogramming Dictates Metastatic Potential in Breast Cancer. Cell Metab. 2015;22:577-89 pubmed publisher
    ..displayed increased HIF-1α activity and expression of the HIF-1α target Pyruvate dehydrogenase kinase-1 (PDK1)...
  65. Tang L, Wu Y, Fang C, Qu P, Gao Z. NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage. Biochem Biophys Res Commun. 2016;469:392-8 pubmed publisher
    ..And miR-375 inhibitor remarkably elevated Pdk1 expression in N2A neurons...
  66. Wang J, Qu D, An J, Yuan G, Liu Y. Integrated microarray analysis provided novel insights to the pathogenesis of glaucoma. Mol Med Rep. 2017;16:8735-8746 pubmed publisher
    ..According to the PPI network, HDAC1, HBN, UBR4 and PDK1 were hub proteins in glaucoma...
  67. Le Good J, Ziegler W, Parekh D, Alessi D, Cohen P, Parker P. Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1. Science. 1998;281:2042-5 pubmed
    ..Thus, the PKB kinase PDK1 may be responsible for the phosphorylation of PKC isotypes...
  68. Wigfield S, Winter S, Giatromanolaki A, Taylor J, Koukourakis M, Harris A. PDK-1 regulates lactate production in hypoxia and is associated with poor prognosis in head and neck squamous cancer. Br J Cancer. 2008;98:1975-84 pubmed publisher
    ..005 split by median). These results indicate that HIF regulation of PDK-1 has a key role in maintaining lactate production in human cancer and that the investigation of PDK-1 inhibitors should be investigated for antitumour effects. ..
  69. Karam M, Legay C, Auclair C, Ricort J. Protein kinase D1 stimulates proliferation and enhances tumorigenesis of MCF-7 human breast cancer cells through a MEK/ERK-dependent signaling pathway. Exp Cell Res. 2012;318:558-69 pubmed publisher
  70. Pópulo H, Caldas R, Lopes J, Pardal J, Máximo V, Soares P. Overexpression of pyruvate dehydrogenase kinase supports dichloroacetate as a candidate for cutaneous melanoma therapy. Expert Opin Ther Targets. 2015;19:733-45 pubmed publisher
    ..Our results suggest that PDK expression may play a role in melanoma development and that DCA can be useful for CM therapy, alone or in combination with mTOR inhibitors. ..
  71. Lee M, Chen G, Puttock E, Wang K, Edwards R, Waterman M, et al. Mathematical modeling links Wnt signaling to emergent patterns of metabolism in colon cancer. Mol Syst Biol. 2017;13:912 pubmed publisher
    ..a self-organizing spatial pattern of glycolysis in xenograft colon tumors where pyruvate dehydrogenase kinase (PDK1), a negative regulator of oxidative phosphorylation, is highly active in clusters of cells arranged in a spotted ..
  72. Peng F, Wang J, Fan W, Meng Y, Li M, Li T, et al. Glycolysis gatekeeper PDK1 reprograms breast cancer stem cells under hypoxia. Oncogene. 2017;: pubmed publisher
    ..Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH+ ..
  73. Zhang Y, Nomura M, Zhong S, Chen N, Bode A, Dong Z. Signal transduction pathways involved in phosphorylation and activation of p70S6K following exposure to UVA irradiation. J Biol Chem. 2001;276:20913-23 pubmed
    ..Moreover, p70(S6K) co-immunoprecipitated with PI 3-kinase and possibly PDK1. The complex possibly possessed a partial basal level of phosphorylation, but not at MAPK sites, which was ..
  74. Ohba T, Watanabe H, Murakami M, Radovanovic M, Iino K, Ishida M, et al. Amlodipine inhibits cell proliferation via PKD1-related pathway. Biochem Biophys Res Commun. 2008;369:376-81 pubmed publisher
    ..These data suggest that PKD1 contributes to the antiproliferative effect of amlodipine on hCASMCs via JAK/STAT signaling and p21((Waf1/Cip1)) up-regulation. ..
  75. Rubio M, Avitabile D, Fischer K, Emmanuel G, Gude N, Miyamoto S, et al. Cardioprotective stimuli mediate phosphoinositide 3-kinase and phosphoinositide dependent kinase 1 nuclear accumulation in cardiomyocytes. J Mol Cell Cardiol. 2009;47:96-103 pubmed publisher
    The phosphoinositide 3-kinase (PI3K)/phosphoinositide dependent kinase 1 (PDK1) signaling pathway exerts cardioprotective effects in the myocardium through activation of key proteins including Akt...
  76. Gagliardi P, di Blasio L, Primo L. PDK1: A signaling hub for cell migration and tumor invasion. Biochim Biophys Acta. 2015;1856:178-88 pubmed publisher
    ..3-Phosphoinositide dependent protein kinase-1 (PDK1 or PDPK1) is an ancient serine-threonine kinase belonging to AGC kinase family...
  77. Fernandez Monreal M, Sánchez Castillo C, Esteban J. APPL1 gates long-term potentiation through its plekstrin homology domain. J Cell Sci. 2016;129:2793-803 pubmed publisher
    ..Interestingly, inhibitors of PDK1 (also known as PDPK1) and Akt have no effect on LTP expression...
  78. Orlacchio A, Ranieri M, Brave M, Arciuch V, Forde T, De Martino D, et al. SGK1 Is a Critical Component of an AKT-Independent Pathway Essential for PI3K-Mediated Tumor Development and Maintenance. Cancer Res. 2017;77:6914-6926 pubmed publisher
    ..Instead, transformation requires the activity of the PDK1-regulated AGC family of protein kinases...
  79. Gudi R, Bowker Kinley M, Kedishvili N, Zhao Y, Popov K. Diversity of the pyruvate dehydrogenase kinase gene family in humans. J Biol Chem. 1995;270:28989-94 pubmed
    Recent evidence from this laboratory indicates that at least two isoenzymic forms of pyruvate dehydrogenase kinase (PDK1 and PDK2) may be involved in the regulation of enzymatic activity of mammalian pyruvate dehydrogenase complex by ..
  80. Jensen C, Buch M, Krag T, Hemmings B, Gammeltoft S, Frodin M. 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1. J Biol Chem. 1999;274:27168-76 pubmed
    ..Here, we show that the isolated N-terminal kinase of RSK2 (amino acids 1-360) is phosphorylated at Ser(227) by PDK1, a constitutively active kinase, leading to 100-fold stimulation of kinase activity...
  81. Seong H, Jung H, Ichijo H, Ha H. Reciprocal negative regulation of PDK1 and ASK1 signaling by direct interaction and phosphorylation. J Biol Chem. 2010;285:2397-414 pubmed publisher
    ..In this study, we reveal a functional association between PDK1 (3-phosphoinositide-dependent protein kinase 1), a critical mediator of cell survival, and ASK1 (apoptosis signal-..
  82. Calleja V, Laguerre M, de Las Heras Martínez G, Parker P, Requejo Isidro J, Larijani B. Acute regulation of PDK1 by a complex interplay of molecular switches. Biochem Soc Trans. 2014;42:1435-40 pubmed publisher
    Phosphoinositide-dependent kinase 1 (PDK1) is the master regulator of at least 23 other AGC kinases whose downstream signalling has often been implicated in various diseases and in particular in cancer...
  83. Wu D, Huang R, Hamanaka R, Krause M, Oh M, Kuo C, et al. HIF-1? is required for disturbed flow-induced metabolic reprogramming in human and porcine vascular endothelium. elife. 2017;6: pubmed publisher
    ..Swine aortic arch endothelia exhibited elevated ROS, NOX4, HIF-1?, and glycolytic enzyme and PDK1 expression, suggesting that DF leads to metabolic reprogramming in vivo...
  84. Meng F, Zhang Y, Li X, Wang J, Wang Z. Clinical significance of miR-138 in patients with malignant melanoma through targeting of PDK1 in the PI3K/AKT autophagy signaling pathway. Oncol Rep. 2017;38:1655-1662 pubmed publisher
    ..promoted cell autophagy, induced LC3 protein expression, and suppressed the PI3K/AKT/mTOR signaling pathway and PDK1 protein expression in A2058 cells...
  85. Ezpeleta J, Boudet Devaud F, Pietri M, Baudry A, Baudouin V, Alleaume Butaux A, et al. Protective role of cellular prion protein against TNF?-mediated inflammation through TACE ?-secretase. Sci Rep. 2017;7:7671 pubmed publisher
    ..localization depends on PrPC modulation of ?1 integrin signaling and downstream activation of ROCK-I and PDK1 kinases...
  86. Xu C, Yu L, Hou J, Jackson R, Wang H, Huang C, et al. Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development. Front Cell Neurosci. 2017;11:330 pubmed publisher
    Decreased expression but increased activity of PDK1 has been observed in neurodegenerative disease...
  87. Peng F, Wang J, Fan W, Meng Y, Li M, Li T, et al. Glycolysis gatekeeper PDK1 reprograms breast cancer stem cells under hypoxia. Oncogene. 2017;: pubmed publisher
    ..This corrects the article DOI: 10.1038/onc.2017.368...
  88. Korotchkina L, Patel M. Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase. J Biol Chem. 2001;276:37223-9 pubmed
    ..site 1 and site 2, however, with different rates in phosphate buffer (for site 1, PDK2 > PDK4 approximately PDK1 > PDK3; for site 2, PDK3 > PDK4 > PDK2 > PDK1). Site 3 was phosphorylated by PDK1 only...
  89. Seong H, Jung H, Ha H. NM23-H1 tumor suppressor physically interacts with serine-threonine kinase receptor-associated protein, a transforming growth factor-beta (TGF-beta) receptor-interacting protein, and negatively regulates TGF-beta signaling. J Biol Chem. 2007;282:12075-96 pubmed
    ..These results suggest that the direct interaction of NM23-H1 and STRAP is important for the regulation of TGF-beta-dependent biological activity as well as NM23-H1 activity. ..
  90. Weisberg E, Banerji L, Wright R, Barrett R, Ray A, Moreno D, et al. Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cells. Blood. 2008;111:3723-34 pubmed publisher
    ..Finally, BAG956 and rapamycin/RAD001 were shown to combine in a nonantagonistic fashion against BCR-ABL- and mutant FLT3-expressing cells both in vitro and in vivo. ..
  91. Xia S, Chen Z, Forman L, Faller D. PKCdelta survival signaling in cells containing an activated p21Ras protein requires PDK1. Cell Signal. 2009;21:502-8 pubmed publisher
    ..anti-apoptotic signals, is activated by phosphotidylinositol 3' kinase/phosphoinositide-dependent kinase 1 (PI(3)K-PDK1) to deliver the survival signal to Akt in the environment of activated p21(Ras)...
  92. Mammano E, Galdi F, Pierobon M, Tessari E, Deng J, Pucciarelli S, et al. Multiplexed protein signal pathway mapping identifies patients with rectal cancer that responds to neoadjuvant treatment. Clin Colorectal Cancer. 2012;11:268-74 pubmed publisher
    ..poor responders; CHK2 and ?-catenin were more highly phosphorylated in poor responders, whereas PDK1 and glycogen synthase kinase (GSK)-3?/? had lower phosphorylation levels in poor responders...