PMID- 21383122
OWN - NLM
STAT- MEDLINE
DCOM- 20110526
LR  - 20230815
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 108
IP  - 12
DP  - 2011 Mar 22
TI  - Nutrient starvation elicits an acute autophagic response mediated by Ulk1 
      dephosphorylation and its subsequent dissociation from AMPK.
PG  - 4788-93
LID - 10.1073/pnas.1100844108 [doi]
AB  - Macroautophagy (herein referred to as autophagy) is an evolutionarily conserved 
      self-digestive process cells adapt to starvation and other stress responses. Upon 
      starvation, autophagy is induced, providing cells with needed nutrient supplies. 
      We report here that Unc-51-like kinase 1 (Ulk1), a key initiator for mammalian 
      autophagy, undergoes dramatic dephosphorylation upon starvation, particularly at 
      serine 638 and serine 758. Phosphorylations of Ulk1 are mediated by mammalian 
      target-of-rapamycin (mTOR) kinase and adenosine monophosphate activated protein 
      kinase (AMPK). AMPK interacts with Ulk1 in a nutrient-dependent manner. Proper 
      phosphorylations on Ulk1 are crucial for Ulk1/AMPK association, as a single 
      serine-to-alanine mutation (S758A) at Ulk1 impairs this interaction. Compared to 
      the wild-type ULK1, this Ulk1-S758A mutant initiates starvation-induced autophagy 
      faster at an early time point, but does not alter the maximum capacity of 
      autophagy when starvation prolongs. This study therefore revealed previously 
      unnoticed acute autophagy response to environmental changes.
FAU - Shang, Libin
AU  - Shang L
AD  - Howard Hughes Medical Institute and Department of Biochemistry, University of 
      Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, 
      TX 75390, USA.
FAU - Chen, She
AU  - Chen S
FAU - Du, Fenghe
AU  - Du F
FAU - Li, Shen
AU  - Li S
FAU - Zhao, Liping
AU  - Zhao L
FAU - Wang, Xiaodong
AU  - Wang X
LA  - eng
GR  - Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110307
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
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 (Ulk1 protein, mouse)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/*metabolism
MH  - Amino Acid Substitution
MH  - Animals
MH  - Autophagy/drug effects/*physiology
MH  - Autophagy-Related Protein-1 Homolog
MH  - Cell Line
MH  - Mice
MH  - Mutation, Missense
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
PMC - PMC3064373
COIS- The authors declare no conflict of interest.
EDAT- 2011/03/09 06:00
MHDA- 2011/05/27 06:00
PMCR- 2011/03/07
CRDT- 2011/03/09 06:00
PHST- 2011/03/09 06:00 [entrez]
PHST- 2011/03/09 06:00 [pubmed]
PHST- 2011/05/27 06:00 [medline]
PHST- 2011/03/07 00:00 [pmc-release]
AID - 1100844108 [pii]
AID - 201100844 [pii]
AID - 10.1073/pnas.1100844108 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4788-93. doi: 
      10.1073/pnas.1100844108. Epub 2011 Mar 7.