The substrate and sequence specificity of the AMP-activated protein kinase. Phosphorylation of glycogen synthase and phosphorylase kinase

Biochim Biophys Acta. 1989 Jun 15;1012(1):81-6. doi: 10.1016/0167-4889(89)90014-1.


In addition to acetyl-CoA carboxylase and HMG-CoA reductase, the AMP-activated protein kinase phosphorylates glycogen synthase, phosphorylase kinase, hormone-sensitive lipase and casein. A number of other substrates for the cyclic AMP-dependent protein kinase, e.g., L-pyruvate kinase and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, are not phosphorylated at significant rates. Examination of the sites phosphorylated on acetyl-CoA carboxylase, hormone-sensitive lipase, glycogen synthase and phosphorylase kinase suggests a consensus recognition sequence in which the serine residue phosphorylated by the AMP-activated protein kinase has a hydrophobic residue on the N-terminal side (i.e., at -1) and at least one arginine residue at -2, -3 or -4. Substrates for cyclic AMP-dependent protein kinase which lack the hydrophobic residue at -1 are not substrates for the AMP-activated protein kinase.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA Carboxylase / metabolism
  • Adenosine Monophosphate / pharmacology*
  • Amino Acid Sequence
  • Animals
  • Caseins / metabolism
  • Cattle
  • Cyclic AMP / pharmacology
  • Enzyme Activation / drug effects
  • Glycogen Synthase / metabolism*
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Kinetics
  • Lipase / metabolism
  • Molecular Sequence Data
  • Phosphorylase Kinase / metabolism*
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Rabbits
  • Rats
  • Substrate Specificity


  • Caseins
  • Adenosine Monophosphate
  • Cyclic AMP
  • Hydroxymethylglutaryl CoA Reductases
  • Glycogen Synthase
  • Protein Kinases
  • Phosphorylase Kinase
  • Lipase
  • Acetyl-CoA Carboxylase