PDK2 Antibody – Rabbit Polyclonal

PDHK2: an atypical protein kinase associated with the mitochondrial matrix. The PDHKs play crucial roles in switching metabolic flux from oxidative phosphorylation towards glycolysis. PDHK2 is expressed in all tissues. 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. 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: EC 2.7.11.2; Protein kinase, atypical; Kinase, protein; Mitochondrial; ATYPICAL group; PDHK family; PDHK subfamily

Cellular Component: nucleoplasm; mitochondrion; cytoplasm; pyruvate dehydrogenase complex; mitochondrial pyruvate dehydrogenase complex

Molecular Function: transferase activity; protein serine/threonine kinase activity; protein binding; protein homodimerization activity; protein heterodimerization activity; nucleotide binding; protein complex binding; kinase activity; pyruvate dehydrogenase (acetyl-transferring) kinase activity; ATP binding

Biological Process: peptidyl-serine phosphorylation; carbohydrate metabolic process; insulin receptor signaling pathway; glucose metabolic process; regulation of pH; cellular response to nutrient; regulation of acetyl-CoA biosynthetic process from pyruvate; regulation of gluconeogenesis; glucose homeostasis; phosphorylation; protein amino acid phosphorylation