Abstract:
: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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Gwinn DM,Shackelford DB,Egan DF,Mihaylova MM,Mery A,Vasquez DS,Turk BE,Shaw RJdoi
10.1016/j.molcel.2008.03.003subject
Has Abstractpub_date
2008-04-25 00:00:00pages
214-26issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(08)00169-Xjournal_volume
30pub_type
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