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Taken together these data support a model where PDHK4 regulates KRAS signalling and its tumorigenic properties and suggest that inhibition of PDHK4 could represent a novel therapeutic strategy to target KRAS mutant colorectal and lung cancers
PDK4 mediates cisplatin-induced acute kidney injury.
Pyruvate dehydrogenase kinase 4 is a direct transcriptional target of FoxO1 (show FOXO1 Proteins) in the heart. FoxO1 (show FOXO1 Proteins) directly regulates Pdk4 transcription in the heart, thereby controlling PDH (show PDP Proteins) activity and subsequent glucose oxidation rates.
inhibition of PDK4 activity in Hepatocellular carcinoma cells increased cyclin E1 (show CCNE1 Proteins), cyclin A2 (show CCNA2 Proteins), and E2F1 (show E2F1 Proteins) proteins.
FXR (show NR1H4 Proteins) may promote the proliferation of tumor cells and the hepatocytes in the process of liver regeneration by activating the PDK4-mediated metabolic reprogramming to generate glycolytic intermediates essential for rapid biomass generation, establishing a mechanistic link between cell proliferation and metabolic switch.
Taken together, our results suggest that LPS (show TLR4 Proteins) induces PDK4 expression and alters glucose metabolism via the JNK (show MAPK8 Proteins) pathway.
upregulation of PDK4 promotes vascular calcification by increasing osteogenic markers with no adverse effect on bone formation, demonstrating that PDK4 is a therapeutic target for vascular calcification.
PDK2 (show PDK2 Proteins)/4 induction and the subsequent lactate surge induce the metabolic shift in the diabetic dorsal root ganglion thereby contributing to the pathogenesis of painful diabetic neuropathy.
Double-knockout mice with global deletion of PDK2 (show PDK2 Proteins) and PDK4, which results in constitutively activated pyruvate dehydrogenase (show PDP Proteins), preferentially oxidize glucose in muscle.
PDK4 promotes tumorigenesis through activation of the CREB (show CREB1 Proteins)-RHEB (show RHEB Proteins)-mTORC1 signaling cascade.
Low PDK4 expression is associated with lung tumorigenesis.
Increased PDK4 expression is associated with colon cancer.
We found that PDK4 gene and protein expression was significantly elevated in pulmonary arterial hypertension pericytes and correlated with reduced mitochondrial metabolism, higher rates of glycolysis, and hyperproliferation
Inhibition of CK2 (show CSNK2A1 Proteins) increased the expression of metabolic regulators, PDK4 and AMPK (show PRKAA1 Proteins) along with the key cellular energy sensor CREB (show CREB1 Proteins).
These findings indicate that the TGFbeta (show TGFB1 Proteins)/PDK4 signaling axis plays an important role in the response of colorectal cancer to chemotherapy.
Combined speed endurance and endurance exercise amplify the exercise-induced PGC-1alpha and PDK4 mRNA response in trained human muscle.
High PDK4 expression is associated with hepatocellular cancer.
Preoperative carbohydrate supplementation was found to ameliorate postoperative insulin (show INS Proteins) sensitivity by reducing muscle inflammatory responses and improved insulin (show INS Proteins) inhibition of FOXO1 (show FOXO1 Proteins)-mediated PDK4 mRNA and protein expression after surgery.
Temporal and spatial expression analysis indicated that porcine PDK4 gene is highly expressed in skeletal muscle and the highest in neonatal pigs.
This gene is a member of the PDK/BCKDK protein kinase family and encodes a mitochondrial protein with a histidine kinase domain. This protein is located in the matrix of the mitrochondria and inhibits the pyruvate dehydrogenase complex by phosphorylating one of its subunits, thereby contributing to the regulation of glucose metabolism. Expression of this gene is regulated by glucocorticoids, retinoic acid and insulin.
pyruvate dehydrogenase kinase 4
, pyruvate dehydrogenase kinase, isoenzyme 4
, pyruvate dehydrogenase kinase, isozyme 4
, [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial
, pyruvate dehydrogenase, lipoamide, kinase isozyme 4, mitochondrial
, pyruvate dehydrogenase kinase isozyme 4
, pyruvate dehydrogenate kinase 4