PMID- 18283331
OWN - NLM
STAT- MEDLINE
DCOM- 20080313
LR  - 20240316
IS  - 1476-5586 (Electronic)
IS  - 1522-8002 (Print)
IS  - 1476-5586 (Linking)
VI  - 10
IP  - 2
DP  - 2008 Feb
TI  - Regulation of mTORC1 signaling by Src kinase activity is Akt1-independent in 
      RSV-transformed cells.
PG  - 99-107
AB  - Increased activity of the Src tyrosine protein kinase that has been observed in a 
      large number of human malignancies appears to be a promising target for drug 
      therapy. In the present study, a critical role of the Src activity in the 
      deregulation of mTOR signaling pathway in Rous sarcoma virus (RSV)-transformed 
      hamster fibroblasts, H19 cells, was shown using these cells treated with the 
      Src-specific inhibitor, SU6656, and clones of fibroblasts expressing either the 
      active Src or the dominant-negative Src kinase-dead mutant. Disruption of the Src 
      kinase activity results in substantial reduction of the phosphorylation and 
      activity of the Akt/protein kinase B (PKB), phosphorylation of tuberin (TSC2), 
      mammalian target of rapamycin (mTOR), S6K1, ribosomal protein S6, and eukaryotic 
      initiation factor 4E-binding protein 4E-BP1. The ectopic, active Akt1 that was 
      expressed in Src-deficient cells significantly enhanced phosphorylation of TSC2 
      in these cells, but it failed to activate the inhibited components of the mTOR 
      pathway that are downstream of TSC2. The data indicate that the Src kinase 
      activity is essential for the activity of mTOR-dependent signaling pathway and 
      suggest that mTOR targets may be controlled by Src independently of Akt1/TSC2 
      cascade in cells expressing hyperactive Src protein. These observations might 
      have an implication in drug resistance to mTOR inhibitor-based cancer therapy in 
      certain cell types.
FAU - Vojtechova, Martina
AU  - Vojtechova M
AD  - Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 
      Prague, Czech Republic.
FAU - Tureckova, Jolana
AU  - Tureckova J
FAU - Kucerova, Dana
AU  - Kucerova D
FAU - Sloncova, Eva
AU  - Sloncova E
FAU - Vachtenheim, Jiri
AU  - Vachtenheim J
FAU - Tuhackova, Zdena
AU  - Tuhackova Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neoplasia
JT  - Neoplasia (New York, N.Y.)
JID - 100886622
RN  - 0 (Indoles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (SU 6656)
RN  - 0 (Sulfonamides)
RN  - EC 2.7.- (Protein Kinases)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - Cricetinae
MH  - Indoles/pharmacology
MH  - Phosphorylation
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Protein Kinases/*metabolism
MH  - Rous sarcoma virus/genetics
MH  - Signal Transduction
MH  - Sulfonamides/pharmacology
PMC - PMC2244684
EDAT- 2008/02/20 09:00
MHDA- 2008/03/14 09:00
PMCR- 2008/02/01
CRDT- 2008/02/20 09:00
PHST- 2007/10/09 00:00 [received]
PHST- 2007/11/15 00:00 [revised]
PHST- 2007/11/15 00:00 [accepted]
PHST- 2008/02/20 09:00 [pubmed]
PHST- 2008/03/14 09:00 [medline]
PHST- 2008/02/20 09:00 [entrez]
PHST- 2008/02/01 00:00 [pmc-release]
AID - 07905 [pii]
AID - 10.1593/neo.07905 [doi]
PST - ppublish
SO  - Neoplasia. 2008 Feb;10(2):99-107. doi: 10.1593/neo.07905.