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Phospholipase D-dependent mTOR complex 1 (mTORC1) activation by glutamine.
Bernfeld, Elyssa; Menon, Deepak; Vaghela, Vishaldeep; Zerin, Ismat; Faruque, Promie; Frias, Maria A; Foster, David A.
Afiliação
  • Bernfeld E; From the Departments of Biological Sciences and.
  • Menon D; the Biochemistry Program and.
  • Vaghela V; From the Departments of Biological Sciences and.
  • Zerin I; the Biochemistry Program and.
  • Faruque P; From the Departments of Biological Sciences and.
  • Frias MA; Biology Program, Graduate Center, City University of New York, New York, New York 10016, and.
  • Foster DA; Chemistry, Hunter College, City University of New York, New York, New York 10065.
J Biol Chem ; 293(42): 16390-16401, 2018 10 19.
Article em En | MEDLINE | ID: mdl-30194281
ABSTRACT
Glutamine is a key nutrient required for sustaining cell proliferation, contributing to nucleotide, protein, and lipid synthesis. The mTOR complex 1 (mTORC1) is a highly conserved protein complex that acts as a sensor of nutrients, relaying signals for the shift from catabolic to anabolic metabolism. Although glutamine plays an important role in mTORC1 activation, the mechanism is not clear. Here we describe a leucine- and Rag-independent mechanism of mTORC1 activation by glutamine that depends on phospholipase D and the production of phosphatidic acid, which is required for the stability and activity of mTORC1. The phospholipase D-dependent activation of mTORC1 by glutamine depended on the GTPases ADP ribosylation factor 1 (Arf1), RalA, and Rheb. Glutamine deprivation could be rescued by α-ketoglutarate, a downstream metabolite of glutamine. This mechanism represents a distinct nutrient input to mTORC1 that is independent of Rag GTPases and leucine.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipase D / Alvo Mecanístico do Complexo 1 de Rapamicina / Glutamina Limite: Humans Idioma: En Revista: J Biol Chem Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipase D / Alvo Mecanístico do Complexo 1 de Rapamicina / Glutamina Limite: Humans Idioma: En Revista: J Biol Chem Ano de publicação: 2018 Tipo de documento: Article