PMID- 25632961
OWN - NLM
STAT- MEDLINE
DCOM- 20150529
LR  - 20220330
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 290
IP  - 11
DP  - 2015 Mar 13
TI  - Reciprocal regulation of AMP-activated protein kinase and phospholipase D.
PG  - 6986-93
LID - 10.1074/jbc.M114.622571 [doi]
AB  - AMP-activated protein kinase (AMPK), a critical sensor of energy sufficiency, 
      acts as central metabolic switch in cell metabolism. Once activated by low energy 
      status, AMPK phosphorylates key regulatory substrates and turns off anabolic 
      biosynthetic pathways. In contrast, the mammalian/mechanistic target of rapamycin 
      (mTOR) is active when there are sufficient nutrients for anabolic reactions. A 
      critical factor regulating mTOR is phosphatidic acid (PA), a central metabolite 
      of membrane lipid biosynthesis and the product of the phospholipase D 
      (PLD)-catalyzed hydrolysis of phosphatidylcholine. PLD is a downstream target of 
      the GTPase Rheb, which is turned off in response to AMPK via the tuberous 
      sclerosis complex. Although many studies have linked AMPK with mTOR, very little 
      is known about the connection between AMPK and PLD. In this report, we provide 
      evidence for reciprocal regulation of PLD by AMPK and regulation of AMPK by PLD 
      and PA. Suppression of AMPK activity led to an increase in PLD activity, and 
      conversely, activation of AMPK suppressed PLD activity. Suppression of PLD 
      activity resulted in elevated AMPK activity. Exogenously supplied PA abolished 
      the inhibitory effects of elevated AMPK activity on mTOR signaling. In contrast, 
      exogenously supplied PA could not overcome the effect AMPK activation if either 
      mTOR or Raptor was suppressed, indicating that the inhibitory effects of PLD and 
      PA on AMPK activity are mediated by mTOR. These data suggest a reciprocal 
      feedback mechanism involving AMPK and the PLD/mTOR signaling node in cancer cells 
      with therapeutic implications.
CI  - (c) 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Mukhopadhyay, Suman
AU  - Mukhopadhyay S
AD  - From the Department of Biological Sciences, Hunter College of the City University 
      of New York, New York, New York 10065.
FAU - Saqcena, Mahesh
AU  - Saqcena M
AD  - From the Department of Biological Sciences, Hunter College of the City University 
      of New York, New York, New York 10065.
FAU - Chatterjee, Amrita
AU  - Chatterjee A
AD  - From the Department of Biological Sciences, Hunter College of the City University 
      of New York, New York, New York 10065.
FAU - Garcia, Avalon
AU  - Garcia A
AD  - From the Department of Biological Sciences, Hunter College of the City University 
      of New York, New York, New York 10065.
FAU - Frias, Maria A
AU  - Frias MA
AD  - From the Department of Biological Sciences, Hunter College of the City University 
      of New York, New York, New York 10065.
FAU - Foster, David A
AU  - Foster DA
AD  - From the Department of Biological Sciences, Hunter College of the City University 
      of New York, New York, New York 10065 foster@genectr.hunter.cuny.edu.
LA  - eng
GR  - RR-03039/RR/NCRR NIH HHS/United States
GR  - R01-CA046677/CA/NCI NIH HHS/United States
GR  - R01-CA179542/CA/NCI NIH HHS/United States
GR  - R01 CA179542/CA/NCI NIH HHS/United States
GR  - R01 CA046677/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150129
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Phosphatidic Acids)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.1.4.4 (Phospholipase D)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Cell Line, Tumor
MH  - Enzyme Activation
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Multiprotein Complexes/metabolism
MH  - Neoplasms/*enzymology/metabolism
MH  - Phosphatidic Acids/metabolism
MH  - Phospholipase D/*metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC4358122
OTO - NOTNLM
OT  - AMP-activated Protein Kinase (AMPK)
OT  - Mammalian Target of Rapamycin (mTOR)
OT  - Phosphatidic Acid
OT  - Phospholipase D (PLD)
OT  - Tuberous Sclerosis Complex (TSC)
EDAT- 2015/01/31 06:00
MHDA- 2015/05/30 06:00
PMCR- 2016/03/13
CRDT- 2015/01/31 06:00
PHST- 2015/01/31 06:00 [entrez]
PHST- 2015/01/31 06:00 [pubmed]
PHST- 2015/05/30 06:00 [medline]
PHST- 2016/03/13 00:00 [pmc-release]
AID - S0021-9258(20)76776-1 [pii]
AID - M114.622571 [pii]
AID - 10.1074/jbc.M114.622571 [doi]
PST - ppublish
SO  - J Biol Chem. 2015 Mar 13;290(11):6986-93. doi: 10.1074/jbc.M114.622571. Epub 2015 
      Jan 29.