Synergistic action of R-Ras and IGF-1 on Bcl-xL expression and caspase-3 inhibition in BaF3 cells: R-Ras and IGF-1 control distinct anti-apoptotic kinase pathways.
R-Ras and insulin-like growth factor-1 (IGF-1) synergistically inhibit apoptosis of BaF3 cells upon interleukin-3 deprivation. To characterize the mechanism of this synergistic inhibition, we examined the effect of R-Ras and IGF-1 on several apoptosis-related proteins. Extracellular signal-regulated kinase (ERK) was activated by IGF-1, but not by R-Ras. In contrast, Akt was activated strongly by R-Ras, but weakly by IGF-1. It was also found that R-Ras and IGF-1 cooperatively induced Bcl-xL expression and inhibited caspase-3 activation.
Suzuki
J
J
Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
Kaziro
Y
Y
Koide
H
H
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D004357:Drug Synergism; D020558:GTP Phosphohydrolases / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051020:bcl-X Protein; D018631:ras Proteins / Q000494:pharmacology*
D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D007334:Insulin-Like Growth Factor I; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020558:GTP Phosphohydrolases; D018631:ras Proteins