PMID- 20940044
OWN - NLM
STAT- MEDLINE
DCOM- 20110415
LR  - 20211203
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 23
IP  - 2
DP  - 2011 Feb
TI  - Lithium induces c-Ret expression in mouse inner medullary collecting duct cells.
PG  - 371-9
LID - 10.1016/j.cellsig.2010.10.007 [doi]
AB  - We found in our present study that lithium (Li(+)) induced the expression of 
      endogenous c-Ret, a tyrosine kinase receptor, in murine inner medullary 
      collecting duct (mIMCD-3) cells. Delineation of the promoter region required for 
      the effect of Li(+) identified a positive regulatory element within 180bp 
      upstream of the transcription initiation site. This region contained three 
      putative GC-rich Sp1 binding sites found to be essential for c-Ret induction by 
      Li(+). The effect of Li(+) was mediated through glycogen synthase kinase 3beta 
      (GSK-3beta) inhibition, although there was no biding site for T cell factor/lymphoid 
      enhancer factor (TCF/LEF) in the 180bp. We found that Li(+) activated the 
      mammalian target of rapamycin (mTOR) pathway via GSK-3beta in these cells, and the 
      effect of Li(+) to induce c-Ret was amenable to the inhibitory effect of the mTOR 
      inhibitor, rapamycin. We also found that alterations in both cellular beta-catenin 
      levels and mTOR activities affected the effect of Li(+) on c-Ret transcription in 
      a cooperative manner. In summary, our results show that Li(+) can induce c-Ret 
      expression in mIMCD-3 cells through both beta-catenin- and mTOR-dependent pathways 
      downstream of GSK-3beta inhibition, which act synergistically on the GC-rich Sp1 
      binding elements in the promoter region.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Kojima, Nobuhiko
AU  - Kojima N
AD  - Medical and Research Services, Greater Los Angeles Veterans Affairs Healthcare 
      System at Sepulveda, North Hills, California, USA. nobuhiko@iis.u-tokyo.ac.jp
FAU - Saito, Hiroshi
AU  - Saito H
FAU - Nishikawa, Masaki
AU  - Nishikawa M
FAU - Yuri, Shunsuke
AU  - Yuri S
FAU - Jo, Oak Don
AU  - Jo OD
FAU - Pham, Phuong-Chi
AU  - Pham PC
FAU - Yanagawa, Naomi
AU  - Yanagawa N
FAU - Yanagawa, Norimoto
AU  - Yanagawa N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101019
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (beta Catenin)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.11.- (Glycogen Synthase Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - G4962QA067 (Lithium Chloride)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - GC Rich Sequence
MH  - Gene Expression Regulation
MH  - Glycogen Synthase Kinases/antagonists & inhibitors
MH  - Kidney Tubules, Collecting/cytology/*drug effects/metabolism
MH  - Lithium Chloride/*pharmacology
MH  - Mice
MH  - Proto-Oncogene Proteins c-ret/*biosynthesis/genetics
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/physiology
MH  - beta Catenin/physiology
EDAT- 2010/10/14 06:00
MHDA- 2011/04/19 06:00
CRDT- 2010/10/14 06:00
PHST- 2010/08/24 00:00 [received]
PHST- 2010/10/01 00:00 [accepted]
PHST- 2010/10/14 06:00 [entrez]
PHST- 2010/10/14 06:00 [pubmed]
PHST- 2011/04/19 06:00 [medline]
AID - S0898-6568(10)00294-9 [pii]
AID - 10.1016/j.cellsig.2010.10.007 [doi]
PST - ppublish
SO  - Cell Signal. 2011 Feb;23(2):371-9. doi: 10.1016/j.cellsig.2010.10.007. Epub 2010 
      Oct 19.