Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase.

Journal Article (Journal Article)

During the evolution of metazoans and the rise of systemic hormonal regulation, the insulin-controlled class 1 phosphatidylinositol 3OH-kinase (PI3K) pathway was merged with the primordial amino acid-driven mammalian target of rapamycin (mTOR) pathway to control the growth and development of the organism. Insulin regulates mTOR function through a recently described canonical signaling pathway, which is initiated by the activation of class 1 PI3K. However, how the amino acid input is integrated with that of the insulin signaling pathway is unclear. Here we used a number of molecular, biochemical, and pharmacological approaches to address this issue. Unexpectedly, we found that a major pathway by which amino acids control mTOR signaling is distinct from that of insulin and that, instead of signaling through components of the insulin/class 1 PI3K pathway, amino acids mediate mTOR activation by signaling through class 3 PI3K, hVps34.

Full Text

Duke Authors

Cited Authors

  • Nobukuni, T; Joaquin, M; Roccio, M; Dann, SG; Kim, SY; Gulati, P; Byfield, MP; Backer, JM; Natt, F; Bos, JL; Zwartkruis, FJT; Thomas, G

Published Date

  • October 4, 2005

Published In

Volume / Issue

  • 102 / 40

Start / End Page

  • 14238 - 14243

PubMed ID

  • 16176982

Pubmed Central ID

  • PMC1242323

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0506925102


  • eng

Conference Location

  • United States