PMID- 21258367
OWN - NLM
STAT- MEDLINE
DCOM- 20110321
LR  - 20240308
IS  - 1476-4679 (Electronic)
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 13
IP  - 2
DP  - 2011 Feb
TI  - AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.
PG  - 132-41
LID - 10.1038/ncb2152 [doi]
AB  - Autophagy is a process by which components of the cell are degraded to maintain 
      essential activity and viability in response to nutrient limitation. Extensive 
      genetic studies have shown that the yeast ATG1 kinase has an essential role in 
      autophagy induction. Furthermore, autophagy is promoted by AMP activated protein 
      kinase (AMPK), which is a key energy sensor and regulates cellular metabolism to 
      maintain energy homeostasis. Conversely, autophagy is inhibited by the mammalian 
      target of rapamycin (mTOR), a central cell-growth regulator that integrates 
      growth factor and nutrient signals. Here we demonstrate a molecular mechanism for 
      regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of 
      yeast ATG1. Under glucose starvation, AMPK promotes autophagy by directly 
      activating Ulk1 through phosphorylation of Ser 317 and Ser 777. Under nutrient 
      sufficiency, high mTOR activity prevents Ulk1 activation by phosphorylating Ulk1 
      Ser 757 and disrupting the interaction between Ulk1 and AMPK. This coordinated 
      phosphorylation is important for Ulk1 in autophagy induction. Our study has 
      revealed a signalling mechanism for Ulk1 regulation and autophagy induction in 
      response to nutrient signalling.
FAU - Kim, Joungmok
AU  - Kim J
AD  - Department of Pharmacology and Moores Cancer Center, University of California at 
      San Diego, La Jolla, CA 92130, USA.
FAU - Kundu, Mondira
AU  - Kundu M
FAU - Viollet, Benoit
AU  - Viollet B
FAU - Guan, Kun-Liang
AU  - Guan KL
LA  - eng
GR  - GM51586/GM/NIGMS NIH HHS/United States
GR  - R01 GM062694/GM/NIGMS NIH HHS/United States
GR  - R01 GM051586/GM/NIGMS NIH HHS/United States
GR  - R01 CA108941/CA/NCI NIH HHS/United States
GR  - GM62694/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110123
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (ULK1 protein, human)
RN  - EC 2.7.11.1 (Ulk1 protein, mouse)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
CIN - Cell Cycle. 2011 May 1;10(9):1337-8. PMID: 21403467
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Autophagy/*physiology
MH  - Autophagy-Related Protein-1 Homolog
MH  - Glucose/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Mice
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Serine/metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC3987946
MID - NIHMS564121
EDAT- 2011/01/25 06:00
MHDA- 2011/03/22 06:00
PMCR- 2014/04/15
CRDT- 2011/01/25 06:00
PHST- 2010/05/05 00:00 [received]
PHST- 2010/12/06 00:00 [accepted]
PHST- 2011/01/25 06:00 [entrez]
PHST- 2011/01/25 06:00 [pubmed]
PHST- 2011/03/22 06:00 [medline]
PHST- 2014/04/15 00:00 [pmc-release]
AID - ncb2152 [pii]
AID - 10.1038/ncb2152 [doi]
PST - ppublish
SO  - Nat Cell Biol. 2011 Feb;13(2):132-41. doi: 10.1038/ncb2152. Epub 2011 Jan 23.