St Vincent's Institute

• Research units

• Structural Biology
• Protein Chemistry and Metabolism
  • Research Themes
  • Honours and PhD Projects
  • Staff
• Molecular Cardiology
• Immunology and Diabetes
• Bone Cell Biology and Disease
• Stem Cell Regulation
• Haematology and Leukaemia
• Molecular Genetics
• Cell Cycle and Cancer
• Cytoskeleton and Cancer
• Pharmacogenomics
• Invasion and Metastasis
• NRL
• Genome Stability

AMPK myristoyl-switching

Project Type

PhD

Summary

We have recently found that Thr172-phosphorylation and activation of AMPK by the upstream kinases CaMKK or LKB1 is stimulated by both AMP and ADP. This initial step in AMPK signaling requires the subunit to be myristoylated and indicates that AMP & ADP may control the myristoyl group exposure by a myristoyl-switching mechanism. The goal of this project is to understand the myristoyl group binding pocket on the heterotrimer and how the myristoyl group is relocated in response to nucleotide binding to the subunit. Exposure of the myristoyl group in response to nucleotide binding may alter the subcellular distribution of AMPK and promote membrane binding (see Oakhill JS, Chen ZP, Scott, JW, Steel R, Castelli LA, Ling N, Macaulay SL and Kemp BE. β-Subunit Myristoylation is the Gatekeeper for Initiating Metabolic Stress Sensing by AMPK. Proc Nat Acad Sci 2010 (in press)).