Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress. ATP + L-seryl-[pyruvate dehydrogenase E1 alpha subunit] = ADP + H(+) + O-phospho-L-seryl-[pyruvate dehydrogenase E1 alpha subunit] Activity is enhanced by binding to the pyruvate dehydrogenase subunit DLAT. Inhibited by AZD7545; this compound interferes with DLAT binding and thereby inhibits kinase activity. Inhibited by dichloroacetate and radicicol. Homodimer, and heterodimer with PDK2. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). Expressed predominantly in the heart. Detected at lower levels in liver, skeletal muscle and pancreas. Up-regulated via the HIF1A signaling pathway in response to hypoxia. Phosphorylated by constitutively activated ABL1, FGFR1, FLT3 and JAK2 (in vitro), and this may also occur in cancer cells that express constitutively activated ABL1, FGFR1, FLT3 and JAK2. Phosphorylation at Tyr-243 and Tyr-244 strongly increases kinase activity, while phosphorylation at Tyr-136 has a lesser effect. Exposure of cancer cells to severe hypoxia induces translocation of AKT to the mitochondrion, leading to AKT-mediated phosphorylation of PDK1 at Thr-346 which supports tumor cell survival and proliferation during hypoxia. Belongs to the PDK/BCKDK protein kinase family.