title: The non-proteinogenic amino acids L-methionine sulfoximine and DL-phosphinothricin activate mTOR.
abstract: L-Methionine sulfoximine (MSO) and DL-Phosphinothricin (PPT), two non-proteinogenic amino acids known as inhibitors of Glutamine Synthetase, cause a dose-dependent increase in the phosphorylation of the mTOR substrate S6 kinase 1. The effect is particularly evident in glutamine-depleted cells, where mTOR activity is very low, but is detectable for PPT also in the presence of glutamine. The stimulation of mTOR activity by either MSO or PPT is strongly synergized by essential amino acids. Thus, the non-proteinogenic amino acids MSO and PPT are mTOR activators.
authors.affiliation: Unit of General and Clinical Pathology, Department of Experimental Medicine, University of Parma, Via Volturno 39, 43125, Parma, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Tardito
authors.forename: Martina
authors.initials: M
authors.lastname: Chiu
authors.forename: Renata
authors.initials: R
authors.lastname: Franchi-Gazzola
authors.forename: Valeria
authors.initials: V
authors.lastname: Dall'Asta
authors.forename: Paola
authors.initials: P
authors.lastname: Comi
authors.forename: Ovidio
authors.initials: O
authors.lastname: Bussolati
mesh_terms: D000613:Aminobutyrates / Q000494:pharmacology*; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008717:Methionine Sulfoximine / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D013237:Stereoisomerism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000613:Aminobutyrates; D005973:Glutamine; D008717:Methionine Sulfoximine; C003121:phosphinothricin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D005974:Glutamate-Ammonia Ligase