PDK1

Pyruvate dehydrogenase (PDH) is a mitochondrial multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate and is one of the major enzymes responsible for the regulation of homeostasis of carbohydrate fuels in mammals. The enzymatic activity is regulated by a phosphorylation/dephosphorylation cycle. Phosphorylation of PDH by a specific pyruvate dehydrogenase kinase (PDK) results in inactivation. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2013]

Pyruvate Dehydrogenase Kinase 1

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.

Cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Glucose metabolic processManual Assertion Based On ExperimentTAS:ProtInc
Hypoxia-inducible factor-1alpha signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Intrinsic apoptotic signaling pathway in response to oxidative stressManual Assertion Based On ExperimentIMP:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Regulation of acetyl-CoA biosynthetic process from pyruvateTAS:Reactome
Regulation of glucose metabolic processManual Assertion Based On ExperimentIMP:UniProtKB

Mitochondrion matrix

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.