AMPK is a highly conserved sensor of cellular energy status that is activated 
under conditions of low intracellular ATP. AMPK responds to energy stress by 
suppressing cell growth and biosynthetic processes, in part through its 
inhibition of the rapamycin-sensitive mTOR (mTORC1) pathway. AMPK 
phosphorylation of the TSC2 tumor suppressor contributes to suppression of 
mTORC1; however, TSC2-deficient cells remain responsive to energy stress. Using 
a proteomic and bioinformatics approach, we sought to identify additional 
substrates of AMPK that mediate its effects on growth control. We report here 
that AMPK directly phosphorylates the mTOR binding partner raptor on two 
well-conserved serine residues, and this phosphorylation induces 14-3-3 binding 
to raptor. The phosphorylation of raptor by AMPK is required for the inhibition 
of mTORC1 and cell-cycle arrest induced by energy stress. These findings uncover 
a conserved effector of AMPK that mediates its role as a metabolic checkpoint 
coordinating cell growth with energy status.