The paper:
S. Jäger et al., “AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha,” Proc Natl Acad Sci, 104(29):12017–22, 2007. (Cited in 106 papers)
The finding:
AMP-activated kinase (AMPK) plays a major role in the regulation of cellular metabolism, increasing gene expression in a variety of metabolic pathways when a cell is energy-deprived, but how it causes these changes was unclear. One target gene, peroxisome-proliferator-activated receptor Υ coactivator 1α (PGC-1α), is another key player in metabolism. By injecting AMPK activators into mice with and without PGC-1α in their skeletal muscle cells (but carrying PGC-1α in other cell types), cellular biochemist Bruce Spiegelman of Harvard Medical School and his colleagues demonstrated that AMPK directly activates PGC-1α —which in turn mediates AMPK’s effects.
The mechanism: Using mass spectrometry analysis, Spiegelman and his colleagues pinpointed two specific locations where AMPK phosphorylates PGC-1α. “It was one of the more ...
