PMID- 16870609
OWN - NLM
STAT- MEDLINE
DCOM- 20061127
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 281
IP  - 39
DP  - 2006 Sep 29
TI  - Nutrient-dependent multimerization of the mammalian target of rapamycin through 
      the N-terminal HEAT repeat region.
PG  - 28605-14
AB  - The mammalian target of rapamycin (mTOR) plays a pivotal role in the regulation 
      of cell growth in response to a variety of signals such as nutrients and growth 
      factors. mTOR forms two distinct complexes in vivo. mTORC1 (mTOR complex 1) is 
      rapamycin-sensitive and regulates the rate of protein synthesis in part by 
      phosphorylating two well established effectors, S6K1 (p70 ribosomal S6 kinase 1) 
      and 4E-BP1 (eukaryotic initiation factor 4E-binding protein 1). mTORC2 is 
      rapamycin-insensitive and likely regulates actin organization and activates 
      Akt/protein kinase B. Here, we show that mTOR forms a multimer via its N-terminal 
      HEAT repeat region in mammalian cells. mTOR multimerization is promoted by amino 
      acid sufficiency, although the state of multimerization does not directly 
      correlate with the phosphorylation state of S6K1. mTOR multimerization was 
      insensitive to rapamycin treatment but hindered by butanol treatment, which 
      inhibits phosphatidic acid production by phospholipase D. We also found that mTOR 
      forms a multimer in both mTORC1 and mTORC2. In addition, Saccharomyces cerevisiae 
      TOR proteins Tor1p and Tor2p also exist as homomultimers. These results suggest 
      that TOR multimerization is a conserved mechanism for TOR functioning.
FAU - Takahara, Terunao
AU  - Takahara T
AD  - Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 
      Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
FAU - Hara, Kenta
AU  - Hara K
FAU - Yonezawa, Kazuyoshi
AU  - Yonezawa K
FAU - Sorimachi, Hiroyuki
AU  - Sorimachi H
FAU - Maeda, Tatsuya
AU  - Maeda T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060726
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Culture Media)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Phosphatidic Acids)
RN  - 0 (Phosphoproteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.4.4 (Phospholipase D)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - COS Cells
MH  - Cell Cycle Proteins
MH  - Chlorocebus aethiops
MH  - Culture Media/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Phosphatidic Acids/pharmacology
MH  - Phospholipase D/metabolism
MH  - Phosphoproteins/metabolism
MH  - Protein Binding
MH  - Protein Kinases/*physiology
MH  - Protein Structure, Tertiary
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Saccharomyces cerevisiae/metabolism
MH  - TOR Serine-Threonine Kinases
EDAT- 2006/07/28 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/07/28 09:00
PHST- 2006/07/28 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/07/28 09:00 [entrez]
AID - S0021-9258(19)33952-3 [pii]
AID - 10.1074/jbc.M606087200 [doi]
PST - ppublish
SO  - J Biol Chem. 2006 Sep 29;281(39):28605-14. doi: 10.1074/jbc.M606087200. Epub 2006 
      Jul 26.