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PMID: 16176982 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 40 ·2005-10-04 ·Pages 14238-43

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

Abstract

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acids/metabolism Blotting, Western Cell Line, Tumor Humans Microscopy, Fluorescence Monomeric GTP-Binding Proteins/genetics Neuropeptides/genetics Phosphatidylinositol 3-Kinases/metabolism Protein Kinases/metabolism Proteins/metabolism RNA, Small Interfering/genetics Ras Homolog Enriched in Brain Protein Regulatory-Associated Protein of mTOR Signal Transduction/physiology TOR Serine-Threonine Kinases
Chemicals
Adaptor Proteins, Signal Transducing Amino Acids Neuropeptides Proteins RHEB protein, human RNA, Small Interfering RPTOR protein, human Ras Homolog Enriched in Brain Protein Regulatory-Associated Protein of mTOR Protein Kinases MTOR protein, human TOR Serine-Threonine Kinases Monomeric GTP-Binding Proteins
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Nobukuni Takahiro
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Joaquin Manel
Roccio Marta
Dann Stephen G
Kim So Young
Gulati Pawan
Byfield Maya P
Backer Jonathan M
Natt Francois
Bos Johannes L
Zwartkruis Fried J T
Thomas George
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0506925102
Published
2005-10-04
Epub
2005-00-21
Pages
14238-43
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1242323
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0506925102 PMC Full Text View journal details
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