 |
|
|
  |
||
|
|||||||||
|
|||||||||||||||||||||||||||
|
Faculty Profile
Address: Phone:
212-305-6314
International
Collaborations Training
Activities |
 |
Research Summary Our research focuses on the Snf1/AMP-activated protein kinase (AMPK) family, which is essential for stress responses in all eukaryotes. In humans, AMPK has broad roles in responses to metabolic stress and has been implicated in type 2 diabetes, obesity, and cardiovascular disease. In the yeast Saccharomyces cerevisiae, Snf1 protein kinase regulates transcription, metabolism, and developmental processes in response to nutrient starvation and other stresses. We are interested in the regulation of Snf1/AMPK pathways, with respect to both catalytic activity and subcellular localization. We identified the first upstream kinases for Snf1/AMPK: three yeast kinases and the mammalian tumor suppressor kinase LKB1 and CaMKK, which activate AMPK. We found that both LKB1 and CaMKK function in yeast to activate Snf1. This heterologous function has provided the basis for a powerful genetic selection in yeast for mammalian AMPK kinases, which are potential therapeutic targets. We are currrently exploiting this selection to identify new AMPK kinases, and we recently identified TGF-beta-activated kinase (TAK1), a member of the MAPKKK family that is activated by cytokines and bacterial lipopolysaccharide. Evidence supports TAK1 as a candidate for an authentic AMPK kinase in mammalian cells, and further studies are underway.Selected Publications 1.
Momcilovic, M., S.-P. Hong, and M.
Carlson. 2006. Mammalian TAK1 activates Snf1 protein kinase in
yeast and phosphorylates AMPK in vitro. J. Biol. Chem. July epub.
2.
Woods, A., K. Dickerson, R. Heath, S.-P. Hong, M. Momcilovic, S. R.
Johnstone, M. Carlson and D.
Carling. 2005. Ca2+/calmodulin-dependent protein kinase kinase- beta
acts upstream of AMP-activated protein kinase in mammalian cells. Cell
Metabolism 2: 21-33. 3.
Hong, S.-P., M. Momcilovic, and M.
Carlson. 2005. Function of mammalian LKB1 and
Ca2+/calmodulin-dependent protein kinase kinase beta as Snf1-activating
kinases in yeast. J. Biol. Chem. 280: 21804-21809.
Current Research 1. Yeast Genetic Selection for Human AMPK Kinases Honors and Awards
Committee/Council Memberships
|
|||||||||||||||||||||||||
|
|
