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PMID: 11069888 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Regulation of cellular growth by the Drosophila target of rapamycin dTOR.

Genes & development ·Vol. 14 ·No. 21 ·2000-11-01 ·Pages 2712-24

Zhang H, Stallock JP, Ng JC, Reinhard C, Neufeld TP

Abstract

The TOR protein kinases (TOR1 and TOR2 in yeast; mTOR/FRAP/RAFT1 in mammals) promote cellular proliferation in response to nutrients and growth factors, but their role in development is poorly understood. Here, we show that the Drosophila TOR homolog dTOR is required cell autonomously for normal growth and proliferation during larval development, and for increases in cellular growth caused by activation of the phosphoinositide 3-kinase (PI3K) signaling pathway. As in mammalian cells, the kinase activity of dTOR is required for growth factor-dependent phosphorylation of p70 S6 kinase (p70(S6K)) in vitro, and we demonstrate that overexpression of p70(S6K) in vivo can rescue dTOR mutant animals to viability. Loss of dTOR also results in cellular phenotypes characteristic of amino acid deprivation, including reduced nucleolar size, lipid vesicle aggregation in the larval fat body, and a cell type-specific pattern of cell cycle arrest that can be bypassed by overexpression of the S-phase regulator cyclin E. Our results suggest that dTOR regulates growth during animal development by coupling growth factor signaling to nutrient availability.

MeSH Terms
Amino Acid Sequence Amino Acids/metabolism Animals Cell Cycle/genetics Cell Division/genetics Cell Size Cyclin E/physiology Drosophila Proteins Drosophila melanogaster/cytology,genetics,growth & development Energy Metabolism/genetics Gene Targeting Genes, Insect Growth Disorders/genetics Humans Insect Proteins/genetics,physiology Larva Molecular Sequence Data Phenotype Phosphatidylinositol 3-Kinases/physiology Phosphorylation Phosphotransferases (Alcohol Group Acceptor)/genetics,physiology Protein Kinases Protein Processing, Post-Translational Ribosomal Protein S6 Kinases/physiology Sequence Alignment Sequence Homology, Amino Acid Signal Transduction Sirolimus/pharmacology TOR Serine-Threonine Kinases
Chemicals
Amino Acids Cyclin E Drosophila Proteins Insect Proteins Protein Kinases Phosphotransferases (Alcohol Group Acceptor) target of rapamycin protein, Drosophila Ribosomal Protein S6 Kinases TOR Serine-Threonine Kinases Sirolimus
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zhang H
Chiron Corporation, Emeryville, California 94608, USA.
Stallock J P
Ng J C
Reinhard C
Neufeld T P
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.835000
Published
2000-11-01
Pages
2712-24
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC317034
Subset
IM
Grants
NCI NIH HHS · P30 CA077598 · United States
NCI NIH HHS · P30 CA77598 · United States
External Links
PubMed source DOI: 10.1101/gad.835000 PMC Full Text View journal details
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