PMID- 21710263
OWN - NLM
STAT- MEDLINE
DCOM- 20120910
LR  - 20211203
IS  - 1438-2199 (Electronic)
IS  - 0939-4451 (Linking)
VI  - 42
IP  - 6
DP  - 2012 Jun
TI  - p70 S6K1 nuclear localization depends on its mTOR-mediated phosphorylation at 
      T389, but not on its kinase activity towards S6.
PG  - 2251-6
LID - 10.1007/s00726-011-0965-4 [doi]
AB  - The protein kinase p70 S6K1 is regulated in response to cytokines, nutrients and 
      growth factors, and plays an important role in the development of a variety of 
      human diseases. Mammalian target of rapamycin (mTOR) is known to phosphorylate 
      and thereby activate p70 S6K1. p70 S6K1 phosphorylates different cytoplasmic and 
      nuclear substrates involved in the regulation of protein synthesis, cell cycle, 
      cell growth and survival. Recently, we have shown that mTOR-mediated 
      phosphorylation of p70 S6K1 at T389 also regulates its nucleocytoplasmic 
      localization. Since this phosphorylation is associated with its kinase activity 
      the question whether p70 S6K1 phosphorylation or kinase activity is essential for 
      its proper localization remained elusive. Recently, the chemical compound 
      PF-4708671 has been demonstrated to block p70 S6K1 kinase activity while inducing 
      its phosphorylation at T389. This potential of PF-4708671 to separate p70 S6K1 
      activity from its T389 phosphorylation allowed us to demonstrate that the proper 
      nucleocytoplasmic localization of this kinase depends on its mTOR-mediated 
      phosphorylation but not on its kinase activity. These findings provide important 
      insights into the regulation of p70 S6K1 and allow a more detailed understanding 
      of subcellular enzyme localization processes.
FAU - Rosner, M
AU  - Rosner M
AD  - Institute of Medical Genetics, Medical University of Vienna, Wahringer Strasse 
      10, 1090, Vienna, Austria.
FAU - Schipany, K
AU  - Schipany K
FAU - Hengstschlager, M
AU  - Hengstschlager M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110628
PL  - Austria
TA  - Amino Acids
JT  - Amino acids
JID - 9200312
RN  - 0 (Imidazoles)
RN  - 0 (PF-4708671)
RN  - 0 (Piperazines)
RN  - 0 (Protein Kinase Inhibitors)
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  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Cell Nucleus/drug effects/*metabolism
MH  - Fibroblasts/cytology/drug effects/*metabolism
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Phosphorylation
MH  - Piperazines/pharmacology
MH  - Primary Cell Culture
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Ribosomal Protein S6 Kinases, 70-kDa/antagonists & inhibitors/*metabolism
MH  - Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
EDAT- 2011/06/29 06:00
MHDA- 2012/09/11 06:00
CRDT- 2011/06/29 06:00
PHST- 2011/05/11 00:00 [received]
PHST- 2011/06/11 00:00 [accepted]
PHST- 2011/06/29 06:00 [entrez]
PHST- 2011/06/29 06:00 [pubmed]
PHST- 2012/09/11 06:00 [medline]
AID - 10.1007/s00726-011-0965-4 [doi]
PST - ppublish
SO  - Amino Acids. 2012 Jun;42(6):2251-6. doi: 10.1007/s00726-011-0965-4. Epub 2011 Jun 
      28.