Interaction of galectin-1 with caveolae induces mouse embryonic stem cell proliferation through the Src, ERas, Akt and mTOR signaling pathways.
Galectins have the potential to provide a promising alternative for unveiling the complexity of embryonic stem (ES) cell self-renewal, although the mechanism by which galectins maintain ES cell self-renewal has yet to be identified. Galectin-1 increased [(3)H]-thymidine incorporation as well as cyclin expression and decreased p27(kip1) expression. Src and caveolin-1 phosphorylation was increased by galectin-1, and phospho-caveolin-1 was inhibited by PP2. In addition, inhibition of caveolin-1 by small interfering RNA and methyl-beta-cyclodextrin (Mbeta-CD) decreased galectin-1-induced cyclin expression and [(3)H]-thymidine incorporation. Galectin-1 caused Akt and mTOR phosphorylation, which is involved in cyclin expression. Galectin-1-induced phospho-Akt and -mTOR was inhibited by PP2, ERas siRNA, caveolin-1 siRNA and Mbeta-CD. Furthermore, mTOR phosphorylation was decreased by LY294002 and Akt inhibitor. Galectin-1-induced increase in cyclin expression and decrease in p27(kip1) was blocked by Akt inhibitor and rapamycin. In conclusion, galectin-1 increased DNA synthesis in mouse ES cells via Src, caveolin-1 Akt, and mTOR signaling pathways.
Lee
M Y
MY
Department of Veterinary Physiology, Biotherapy Human Resources Center, Chonnam National University, Gwangju, Korea.
Lee
S H
SH
Park
J H
JH
Han
H J
HJ
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D049109:Cell Proliferation; D004247:DNA / Q000096:biosynthesis; D053595:Embryonic Stem Cells / Q000166:cytology*; D037483:Galectin 1 / Q000378:metabolism*; D051379:Mice; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D019061:src-Family Kinases / Q000378:metabolism
D002352:Carrier Proteins; D051242:Caveolin 1; C474773:ERas protein, mouse; D037483:Galectin 1; D004247:DNA; D017853:Phosphotransferases (Alcohol Group Acceptor); C546842:MTOR protein, human; C546843:mTOR protein, mouse; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D015689:Oncogene Protein p21(ras)