PMID- 10971657
OWN - NLM
STAT- MEDLINE
DCOM- 20001107
LR  - 20211203
IS  - 1356-9597 (Print)
IS  - 1356-9597 (Linking)
VI  - 5
IP  - 9
DP  - 2000 Sep
TI  - Carboxyl-terminal region conserved among phosphoinositide-kinase-related kinases 
      is indispensable for mTOR function in vivo and in vitro.
PG  - 765-75
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) belongs to the family of 
      phosphoinositide (PI)-kinase-related kinases that includes the 
      ataxia-telangiectasia gene product (ATM). mTOR plays a critical role in 
      controlling translational effectors such as p70 S6 kinase alpha (p70 alpha) and 
      eukaryotic initiation factor 4E binding protein 1 (4EBP1). RESULTS: We show that 
      the C-terminal region of mTOR, which is highly conserved among the 
      PI-kinase-related kinases, plays a critical role in the mTOR protein kinase 
      activity. Deletion of the C-terminal residues did not adversely affect the 
      expression of mTOR, but caused a nearly complete loss of the mTOR protein kinase 
      activity toward both 4EBP1 and p70 alpha in vitro. These deletions also abolished 
      the ability of a rapamycin-resistant mTOR mutant to rescue the activity of p70 
      alpha from inhibition induced by rapamycin in vivo. Furthermore, replacement of 
      Trp2545, a conserved residue in the C-terminal region throughout the 
      PI-kinase-related kinase family, abolished the function of the mTOR kinase, both 
      in vivo and in vitro. However, substitution of 32 C-terminal residues of mTOR 
      with those of ATM did not restore the mTOR function. CONCLUSIONS: These findings 
      define an indispensable role for the noncatalytic C-terminal region of mTOR and 
      indicate that, although this highly conserved region may be important throughout 
      the PI-kinase-related kinase family, it is not functionally interchangeable 
      within the family.
FAU - Takahashi, T
AU  - Takahashi T
AD  - Biosignal Research Center, Kobe University, Kobe 657-8501, Japan.
FAU - Hara, K
AU  - Hara K
FAU - Inoue, H
AU  - Inoue H
FAU - Kawa, Y
AU  - Kawa Y
FAU - Tokunaga, C
AU  - Tokunaga C
FAU - Hidayat, S
AU  - Hidayat S
FAU - Yoshino, K
AU  - Yoshino K
FAU - Kuroda, Y
AU  - Kuroda Y
FAU - Yonezawa, K
AU  - Yonezawa K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Genes Cells
JT  - Genes to cells : devoted to molecular & cellular mechanisms
JID - 9607379
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Peptide Initiation Factors)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
EIN - Genes Cells 2000 Nov;5(11):949-52
MH  - Amino Acid Sequence
MH  - Cell Line
MH  - Conserved Sequence
MH  - Eukaryotic Initiation Factor-4E
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Peptide Initiation Factors/metabolism
MH  - Phosphorylation
MH  - Phosphotransferases (Alcohol Group Acceptor)/chemistry/*metabolism
MH  - *Protein Kinases
MH  - Ribosomal Protein S6 Kinases/*metabolism
MH  - Sequence Alignment
MH  - Sequence Deletion
MH  - Sirolimus/metabolism/pharmacology
MH  - TOR Serine-Threonine Kinases
EDAT- 2000/09/06 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/09/06 11:00
PHST- 2000/09/06 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/09/06 11:00 [entrez]
AID - gtc365 [pii]
AID - 10.1046/j.1365-2443.2000.00365.x [doi]
PST - ppublish
SO  - Genes Cells. 2000 Sep;5(9):765-75. doi: 10.1046/j.1365-2443.2000.00365.x.