Initiation factor eIF2B not p70 S6 kinase is involved in the activation of the PI-3K signalling pathway induced by the v-src oncogene.
Our data show that in hamster fibroblasts transformed by Rous sarcoma virus (RSV), the phosphoinositide 3'-kinase (PI-3K)/Akt/glycogen synthase kinase 3 antiapoptotic pathway is upregulated and involved in increased protein synthesis through activation of initiation factor eIF2B. Upon inhibition of PI-3K by wortmannin, phosphorylation of 70-kDa ribosomal protein S6 kinase (p70 S6k) and its physiological substrate, ribosomal protein S6, decreased in the non-transformed cells but not in RSV-transformed cells. Thus PI-3K, which is thought to be involved in regulation of p70 S6k, signals to p70 S6k in normal fibroblasts, but it does not appear to be an upstream effector of p70 S6k in fibroblasts transformed by v-src oncogene, suggesting that changes in the PI-3K signalling pathway upstream of p70 S6k are induced by RSV transformation.
Vojtechová
Martina
M
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 16637 6, Prague, Czech Republic.
Sloncová
Eva
E
Kucerová
Dana
D
Jiricka
Jaroslav
J
Sovová
Vlasta
V
Tuhácková
Zdena
Z
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics / Q000472:pathogenicity; D002460:Cell Line; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D006224:Cricetinae; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020717:Eukaryotic Initiation Factor-2B / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology*; D015398:Signal Transduction; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D020717:Eukaryotic Initiation Factor-2B; D038362:Glycogen Synthase Kinase 3; D015688:Oncogene Protein pp60(v-src); D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D000077191:Wortmannin