Poster Presentation Melbourne Protein Group Student Symposium 2013

Characterisation of Compound Induced Phosphatase Resistance of AMPK (#24)

Toby Dite 1 , Jon Oakhill 1 , Bruce Kemp 1
  1. St Vincent's Institute of Medical Research, Fitzroy, VIC, Australia

AMP-activated protein kinase (AMPK) regulates cellular energy consumption during metabolic stress by activating catabolic processes and inhibiting anabolic processes. Current first-line therapeutics for diabetes indirectly activate AMPK, which in turn lowers plasma glucose and inhibits lipid synthesis1 . Dephosphorylation of the activation loop of AMPK has been identified as a main mechanism of AMPK inhibition2 , and phosphatase inhibition reverses the diabetic phenotype in some cells3 . Novel compounds have been characterised here by their ability to induce resistance to dephosphorylation by the phosphatase PPM1A at the activation loop.

  1. Steinberg, G.R. & Kemp, B.E. AMPK in Health and Disease. Physiol Rev 89, 1025-1078 (2009)
  2. Suzuki, T. et al. Inhibition of AMPK Catabolic Action by GSK3. Mol Cell 50, 407-19 (2013)
  3. Wang, X.R., et al. AMP-activated protein kinase rescues the angiogenic functions of endothelial progenitor cells via manganese superoxide dismutase induction in type 1 diabetes. Am J Physiol Endocrinol Metab 300, E1135-45 (2011)