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PDK1

Function

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.

Post-translational modifications

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.

Sequence similarities

Belongs to the PDK/BCKDK protein kinase family.

Tissue specificity

Expressed predominantly in the heart. Detected at lower levels in liver, skeletal muscle and pancreas.

Cellular localization

  • Mitochondrion matrix

Alternative names

  • Pyruvate dehydrogenase kinase isoform 1
  • PDH kinase 1
  • PDK1
  • PDHK1

Target type

Proteins

Molecular weight

49244Da