PMID- 12000755
OWN - NLM
STAT- MEDLINE
DCOM- 20020916
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 31
DP  - 2002 Aug 2
TI  - Predominant nuclear localization of mammalian target of rapamycin in normal and 
      malignant cells in culture.
PG  - 28127-34
AB  - Mammalian target of rapamycin (mTOR) controls initiation of translation through 
      regulation of ribosomal p70S6 kinase (S6K1) and eukaryotic translation initiation 
      factor-4E (eIF4E) binding protein (4E-BP). mTOR is considered to be located 
      predominantly in cytosolic or membrane fractions and may shuttle between the 
      cytoplasm and nucleus. In most previous studies a single cell line, 
      E1A-immortalized human embryonic kidney cells (HEK293), has been used. Here we 
      show that in human malignant cell lines, human fibroblasts, and murine myoblasts 
      mTOR is predominantly nuclear. In contrast, mTOR is largely excluded from the 
      nucleus in HEK293 cells. Hybrids between HEK293 and Rh30 rhabdomyosarcoma cells 
      generated cells co-expressing markers unique to HEK293 (E1A) and Rh30 (MyoD). 
      mTOR distribution was mainly nuclear with detectable levels in the cytoplasm. 
      mTOR isolated from Rh30 nuclei phosphorylated recombinant GST-4E-BP1 (Thr-46) in 
      vitro and thus has kinase activity. We next investigated the cellular 
      distribution of mTOR substrates 4E-BP, S6K1, and eIF4E. 4E-BP was exclusively 
      detected in cytoplasmic fractions in all cell lines. S6K1 was localized in the 
      cytoplasm in colon carcinoma, HEK293 cells, and IMR90 fibroblasts. S6K1 was 
      readily detected in all cellular fractions derived from rhabdomyosarcoma cells. 
      eIF4E was detected in all fractions derived from rhabdomyosarcoma cells but was 
      not detectable in nuclear fractions from colon carcinoma HEK293 or IMR90 cells.
FAU - Zhang, Xiongwen
AU  - Zhang X
AD  - Department of Molecular Pharmacology, St. Jude Children's Research Hospital, 
      Memphis, Tennessee 38105-2794, USA.
FAU - Shu, Lili
AU  - Shu L
FAU - Hosoi, Hajime
AU  - Hosoi H
FAU - Murti, K Gopal
AU  - Murti KG
FAU - Houghton, Peter J
AU  - Houghton PJ
LA  - eng
GR  - CA23099/CA/NCI NIH HHS/United States
GR  - CA28765/CA/NCI NIH HHS/United States
GR  - CA77776/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020508
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal
MH  - Cell Line
MH  - Cell Nucleus/*physiology
MH  - Humans
MH  - Kidney
MH  - Mice
MH  - Protein Kinases/analysis/*metabolism
MH  - Recombinant Proteins/analysis/metabolism
MH  - Rhabdomyosarcoma
MH  - TOR Serine-Threonine Kinases
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 2002/05/10 10:00
MHDA- 2002/09/17 10:01
CRDT- 2002/05/10 10:00
PHST- 2002/05/10 10:00 [pubmed]
PHST- 2002/09/17 10:01 [medline]
PHST- 2002/05/10 10:00 [entrez]
AID - S0021-9258(19)66283-6 [pii]
AID - 10.1074/jbc.M202625200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Aug 2;277(31):28127-34. doi: 10.1074/jbc.M202625200. Epub 2002 
      May 8.