Reciprocal regulation of AMP-activated protein kinase and phospholipase D
Authors: Suman Mukhopadhyay
Mahesh Saqcena
David A Foster
Maria A Frias
Avalon Garcia
Amrita Chatterjee
Journal: Journal of Biological Chemistry (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: AMP-activated Protein Kinase (AMPK); Mammalian Target of Rapamycin (mTOR); Phosphatidic Acid; Phospholipase D (PLD); Tuberous Sclerosis Complex (TSC).
Affiliations: From the Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10065., From the Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10065 .

Abstract:  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. 

Retracted: No

PubPeer comments:
 This Elsevier article contains several [tortured phrases] that make some passages hard to parse: * **cardiovascular breakdown** instead of the established _u2018heart failureu2019_ * **computerized reasoning** instead of the established _u2018artificial intelligenceu2019_ * **counterfeit neural** instead of the established _u2018artificial neural (network)u2019_ * **fake neural** instead of the established _u2018artificial neural (network)u2019_ * **fluffy set** instead of the established _u2018fuzzy setu2019_ * **hereditary algorithm** instead of the established _u2018genetic algorithmu2019_ * **man-made consciousness** instead of the established _u2018artificial intelligenceu2019_ Can the authors explain why they departed from the established phrases? ![file] ![file] ![file] How come these incorrect wordings survived proofreading by the coauthors, editors, referees, copy editors, and typesetters? Found with the [_Problematic Paper Screener_] . ,