PMID- 21336308
OWN - NLM
STAT- MEDLINE
DCOM- 20110427
LR  - 20211203
IS  - 1476-4679 (Electronic)
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 13
IP  - 3
DP  - 2011 Mar
TI  - Inactivation of Rheb by PRAK-mediated phosphorylation is essential for 
      energy-depletion-induced suppression of mTORC1.
PG  - 263-72
LID - 10.1038/ncb2168 [doi]
AB  - Cell growth can be suppressed by stressful environments, but the role of stress 
      pathways in this process is largely unknown. Here we show that a cascade of p38beta 
      mitogen-activated protein kinase (MAPK) and p38-regulated/activated kinase (PRAK) 
      plays a role in energy-starvation-induced suppression of mammalian target of 
      rapamycin (mTOR), and that energy starvation activates the p38beta-PRAK cascade. 
      Depletion of p38beta or PRAK diminishes the suppression of mTOR complex 1 (mTORC1) 
      and reduction of cell size induced by energy starvation. We show that p38beta-PRAK 
      operates independently of the known mTORC1 inactivation pathways--phosphorylation 
      of tuberous sclerosis protein 2 (TSC2) and Raptor by AMP-activated protein kinase 
      (AMPK)--and surprisingly, that PRAK directly regulates Ras homologue enriched in 
      brain (Rheb), a key component of the mTORC1 pathway, by phosphorylation. 
      Phosphorylation of Rheb at Ser 130 by PRAK impairs the nucleotide-binding ability 
      of Rheb and inhibits Rheb-mediated mTORC1 activation. The direct regulation of 
      Rheb by PRAK integrates a stress pathway with the mTORC1 pathway in response to 
      energy depletion.
CI  - (c) 2011 Macmillan Publishers Limited. All rights reserved.
FAU - Zheng, Min
AU  - Zheng M
AD  - The Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell 
      Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, 
      China.
FAU - Wang, Yan-Hai
AU  - Wang YH
FAU - Wu, Xiao-Nan
AU  - Wu XN
FAU - Wu, Su-Qin
AU  - Wu SQ
FAU - Lu, Bao-Ju
AU  - Lu BJ
FAU - Dong, Meng-Qiu
AU  - Dong MQ
FAU - Zhang, Hongbing
AU  - Zhang H
FAU - Sun, Peiqing
AU  - Sun P
FAU - Lin, Sheng-Cai
AU  - Lin SC
FAU - Guan, Kun-Liang
AU  - Guan KL
FAU - Han, Jiahuai
AU  - Han J
LA  - eng
GR  - AI68896./AI/NIAID NIH HHS/United States
GR  - R01 GM062694/GM/NIGMS NIH HHS/United States
GR  - R01 AI041637-13/AI/NIAID NIH HHS/United States
GR  - AI41637/AI/NIAID NIH HHS/United States
GR  - R01 CA106768/CA/NCI NIH HHS/United States
GR  - R01 AI068896/AI/NIAID NIH HHS/United States
GR  - R01 AI068896-04/AI/NIAID NIH HHS/United States
GR  - R01 AI041637/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110220
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Neuropeptides)
RN  - 0 (Proteins)
RN  - 0 (RHEB protein, human)
RN  - 0 (Ras Homolog Enriched in Brain Protein)
RN  - 0 (Rheb protein, mouse)
RN  - 6YHG2VE3IX (MAP-kinase-activated kinase 5)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Cell Proliferation
MH  - Fibroblasts/cytology
MH  - *Gene Expression Regulation, Enzymologic
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Isoelectric Focusing/methods
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice
MH  - Monomeric GTP-Binding Proteins/*metabolism
MH  - Multiprotein Complexes
MH  - Neuropeptides/*metabolism
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proteins/*metabolism
MH  - RNA Interference
MH  - Ras Homolog Enriched in Brain Protein
MH  - TOR Serine-Threonine Kinases
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC3070924
MID - NIHMS259321
EDAT- 2011/02/22 06:00
MHDA- 2011/04/28 06:00
PMCR- 2011/09/01
CRDT- 2011/02/22 06:00
PHST- 2010/04/30 00:00 [received]
PHST- 2010/12/12 00:00 [accepted]
PHST- 2011/02/22 06:00 [entrez]
PHST- 2011/02/22 06:00 [pubmed]
PHST- 2011/04/28 06:00 [medline]
PHST- 2011/09/01 00:00 [pmc-release]
AID - ncb2168 [pii]
AID - 10.1038/ncb2168 [doi]
PST - ppublish
SO  - Nat Cell Biol. 2011 Mar;13(3):263-72. doi: 10.1038/ncb2168. Epub 2011 Feb 20.