PMID- 30237786
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 9
DP  - 2018
TI  - Real Talk: The Inter-play Between the mTOR, AMPK, and Hexosamine Biosynthetic 
      Pathways in Cell Signaling.
PG  - 522
LID - 10.3389/fendo.2018.00522 [doi]
LID - 522
AB  - O-linked N-acetylglucosamine, better known as O-GlcNAc, is a sugar 
      post-translational modification participating in a diverse range of cell 
      functions. Disruptions in the cycling of O-GlcNAc mediated by O-GlcNAc 
      transferase (OGT) and O-GlcNAcase (OGA), respectively, is a driving force for 
      aberrant cell signaling in disease pathologies, such as diabetes, obesity, 
      Alzheimer's disease, and cancer. Production of UDP-GlcNAc, the metabolic 
      substrate for OGT, by the Hexosamine Biosynthetic Pathway (HBP) is controlled by 
      the input of amino acids, fats, and nucleic acids, making O-GlcNAc a key 
      nutrient-sensor for fluctuations in these macromolecules. The mammalian target of 
      rapamycin (mTOR) and AMP-activated protein kinase (AMPK) pathways also 
      participate in nutrient-sensing as a means of controlling cell activity and are 
      significant factors in a variety of pathologies. Research into the individual 
      nutrient-sensitivities of the HBP, AMPK, and mTOR pathways has revealed a complex 
      regulatory dynamic, where their unique responses to macromolecule levels 
      coordinate cell behavior. Importantly, cross-talk between these pathways 
      fine-tunes the cellular response to nutrients. Strong evidence demonstrates that 
      AMPK negatively regulates the mTOR pathway, but O-GlcNAcylation of AMPK lowers 
      enzymatic activity and promotes growth. On the other hand, AMPK can phosphorylate 
      OGT leading to changes in OGT function. Complex sets of interactions between the 
      HBP, AMPK, and mTOR pathways integrate nutritional signals to respond to changes 
      in the environment. In particular, examining these relationships using systems 
      biology approaches might prove a useful method of exploring the complex nature of 
      cell signaling. Overall, understanding the complex interactions of these nutrient 
      pathways will provide novel mechanistic information into how nutrients influence 
      health and disease.
FAU - Cork, Gentry K
AU  - Cork GK
AD  - Department of Biochemistry and Molecular Biology, University of Kansas Medical 
      Center, Kansas City, KS, United States.
AD  - Department of Pathology, University of Kansas Medical Center, Kansas City, KS, 
      United States.
FAU - Thompson, Jeffrey
AU  - Thompson J
AD  - Department of Biostatistics, University of Kansas Medical Center, Kansas City, 
      KS, United States.
FAU - Slawson, Chad
AU  - Slawson C
AD  - Department of Biochemistry and Molecular Biology, University of Kansas Medical 
      Center, Kansas City, KS, United States.
LA  - eng
GR  - P30 GM122731/GM/NIGMS NIH HHS/United States
GR  - R01 DK100595/DK/NIDDK NIH HHS/United States
GR  - R03 CA223949/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20180906
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
PMC - PMC6136272
OTO - NOTNLM
OT  - AMPK 5' AMP-activated protein kinase
OT  - O-GlcNAc
OT  - OGA
OT  - OGT
OT  - mTOR (mammalian target of rapamycin)
EDAT- 2018/09/22 06:00
MHDA- 2018/09/22 06:01
PMCR- 2018/01/01
CRDT- 2018/09/22 06:00
PHST- 2018/06/22 00:00 [received]
PHST- 2018/08/21 00:00 [accepted]
PHST- 2018/09/22 06:00 [entrez]
PHST- 2018/09/22 06:00 [pubmed]
PHST- 2018/09/22 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2018.00522 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2018 Sep 6;9:522. doi: 10.3389/fendo.2018.00522. 
      eCollection 2018.