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mTORC2 Regulation of the Hexosamine Biosynthetic Pathway (HBP) in Response to Nutrients
Author(s) -
VegaCotto Nicole Marie,
Moloughney Joseph,
Kim Peter,
Wu ChangChih,
Lynch Thomas,
Zhang Sisi,
Adlam Matthew,
Guntaka Sai,
Chou PoChien,
Rabinowitz Joshua D.,
Werlen Guy,
Jacinto Estela
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.633.5
Subject(s) - mtorc2 , mtorc1 , pi3k/akt/mtor pathway , microbiology and biotechnology , nutrient sensing , biology , effector , biochemistry , glutamine , signal transduction , amino acid
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that forms two distinct protein complexes, mTORC1 and mTORC2. mTORC1 has emerged as a central controller of cell metabolism. The role of mTORC2 in cell metabolism is less clear, but so far it has been shown to be involved in the regulation of actin cytoskeleton organization, cell growth and proliferation, and cell survival. The extracellular signals that regulate mTORC2 and its downstream targets remain to be elucidated. In a screen to identify mTORC2 targets or effectors, our lab identified glutamine:fructose‐6‐phosphate amidotransferase (GFAT1) as a physical interactor of mTOR. GFAT1 is the rate limiting enzyme of the hexosamine biosynthetic pathway (HBP). The HBP utilizes glucose metabolites and glutamine as substrates to produce UDP‐GlcNAc, which is used for protein glycosylation. We found that mTORC2 is involved in regulating GFAT1 expression and the HBP. Metabolomics analysis of mTORC2‐disrupted cells also revealed defects in metabolites of the HBP. Our preliminary findings reveal that mTORC2 could regulate GFAT1 in response to the levels of nutrient metabolites. Our studies provide insights on how mTORC2 regulates a biosynthetic pathway in response to nutrients. Support or Funding Information NCI