PDK1 sirna
PDK1 siRNA (Mouse)
NCBI and Uniprot Product Information
Uniprot Description
PDHK1: an ubiquitously expressed, atypical protein kinase associated with the mitochondrial matrix. The PDHKs play crucial roles in switching metabolic flux from oxidative phosphorylation towards glycolysis. PDHK1 is detected in heart, pancreatic islets, and skeletal muscles. Contains a HATPase_c catalytic domain, found in several ATP-binding proteins including protein histidine kinases (PHKs), PHDKs, DNA gyrase B, topoisomerases, heat shock proteins, and DNA mismatch repair proteins. PDHK regulates glucose oxidation through inhibitory phosphorylation of the E1 alpha subunit of the mitochondrial pyruvate dehydrogenase complex (PDHC) at any one of 3 inhibitory serine residues. Inhibitory sites 1, 2, and 3 correspond to S293, S300, and S232 in human PDHA1, respectively. Four PDHK isoenzymes have been described, each with different site specificity: all four phosphorylate sites 1 and 2 but at different rates; for site 1 PDHK2 >PDHK4 >PDHK1 >PDHK3; for site 2, PDHK3> PDHK4 > PDHK2 > PDHK1. Only PDHK1 phosphorylates site 3. PDHKs are recruited to the PDHC by binding to a lipoyl group covalently attached to the inner lipoyl domain of the E2 component. PDHA1 deficiency is the most common enzyme defect in patients with primary lactic acidosis. PDHK1 is a direct HIF-1 target gene. Suppression of PDH by PDHK inhibits the conversion of pyruvate to acetyl-CoA, attenuates mitochondrial respiration, and may contribute to the increased lactate production observed in many tumors. The PDH pathway is repressed in a majority of non-small cell lung carcinomas. Inhibited by AZD7545, dichloroacetate (DCA) and radicicol. Radicicol inhibits kinase activity by binding directly to the ATP-binding pocket of PDHK, similar to HSP90 from the same ATPase/kinase superfamily.
Protein type: Kinase, protein; EC 2.7.11.2; Mitochondrial; Protein kinase, atypical; ATYPICAL group; PDHK family
Cellular Component: mitochondrion; plasma membrane; pyruvate dehydrogenase complex; intracellular; mitochondrial pyruvate dehydrogenase complex
Molecular Function: transferase activity; protein serine/threonine kinase activity; protein homodimerization activity; protein heterodimerization activity; protein complex binding; nucleotide binding; kinase activity; pyruvate dehydrogenase (acetyl-transferring) kinase activity; ATP binding; protein kinase activity
Biological Process: cell proliferation; peptidyl-serine phosphorylation; cell surface receptor linked signal transduction; carbohydrate metabolic process; glucose metabolic process; regulation of acetyl-CoA biosynthetic process from pyruvate; phosphorylation; protein amino acid phosphorylation; induction of apoptosis by oxidative stress