PMID- 19182527
OWN - NLM
STAT- MEDLINE
DCOM- 20090330
LR  - 20211203
IS  - 1551-4005 (Electronic)
IS  - 1551-4005 (Linking)
VI  - 8
IP  - 4
DP  - 2009 Feb 15
TI  - Evaluation of mTOR function by a gain-of-function approach.
PG  - 573-9
AB  - The mammalian target of rapamycin (mTOR), a member of the phosphoinositide 
      3-kinase related kinase (PIKK) family, plays a central role in the regulation of 
      cell growth. The cellular function of mTOR has been proposed based solely on 
      loss-of-function analyses using the specific inhibitor rapamycin or RNAi-mediated 
      knockdown. There have been recent reports of mTOR mutants with enhanced activity 
      that were isolated by genetic screening in yeast. These isolated mTOR mutants 
      exhibited enhanced kinase activity in vitro, and when expressed in cells, 
      prevented the dephosphorylation of known mTOR substrates. The application of 
      these mutants in gain-of-function analyses has enabled a re-evaluation of the 
      function of mTOR. Although these studies confirmed many of the proposed mTOR 
      functions some unexpected observations urged a reconsideration of the regulatory 
      mechanisms and the physiological function of the mTOR pathway. Hyperactive mTOR 
      mutants are thus valuable tools for analysis of the activation mechanism as well 
      as the in vivo function of mTOR.
FAU - Ohne, Yoichiro
AU  - Ohne Y
AD  - Institute of Molecular and Cellular Biosciences, The University of Tokyo, 
      Bunkyo-ku, Tokyo, Japan.
FAU - Takahara, Terunao
AU  - Takahara T
FAU - Maeda, Tatsuya
AU  - Maeda T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090218
PL  - United States
TA  - Cell Cycle
JT  - Cell cycle (Georgetown, Tex.)
JID - 101137841
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Humans
MH  - Mutation
MH  - Protein Kinases/genetics/*metabolism
MH  - *RNA Interference
MH  - Saccharomyces cerevisiae/genetics/metabolism
MH  - Sirolimus/*metabolism
MH  - TOR Serine-Threonine Kinases
EDAT- 2009/02/03 09:00
MHDA- 2009/03/31 09:00
CRDT- 2009/02/03 09:00
PHST- 2009/02/03 09:00 [entrez]
PHST- 2009/02/03 09:00 [pubmed]
PHST- 2009/03/31 09:00 [medline]
AID - 7660 [pii]
AID - 10.4161/cc.8.4.7660 [doi]
PST - ppublish
SO  - Cell Cycle. 2009 Feb 15;8(4):573-9. doi: 10.4161/cc.8.4.7660. Epub 2009 Feb 18.