| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Takayuki Kobe University, Faculty of Medicine, Research Associate, 医学部, 助手 (10166671)
KAIBUCHI Kozo Kobe University, Faculty of Medicine, Research Associate, 医学部, 助手 (00169377)
KAWAHARA Yasuhiro Kobe University, Faculty of Medicine, Research Associate, 医学部, 助手 (80169755)
KANO Yoshio Kobe University, Faculty of Medicine, Research Associate, 医学部, 助手 (70116200)
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| Research Abstract |
It is well known that expression of some nuclear genes is regulated by extracellular signals through their cell surface receptors. However, the mechanisms of signaling from the cell surface receptors to the nuclear genes have not been substantially clarified. In this research project, we have investigated the mechanisms of signaling from the receptors for PDGF, FGF, prostaglandin <E_1> ( <PGE_1> ) and EGF to the c-myc and c-fos genes in Swiss 3T3 cells. PDGF, FGF, <PGE_1> and EGF are potent growth factors for this cell line. The c-myc and c-fos genes have been suggested to be responsible for the transition from the <G_0> to <G_1> phase of the cell cycle in Balb/c 3T3 cells. Our series of experiments have revealed that PDGF and FGF activate the c-myc and c-fos genes through the protein kinase C activation and <Ca^(2+)> mobilization, both of which are induced by the phospholipase C-mediated hydrolysis of phosphoinositides in a receptor-linked manner. In contrast, <PGE_1> activates these genes through cyclic AMP production and <Ca^(2+)> influx. In the case of EGF, this growth factor also activates these genes, but the signaling mechanism of this growth factor is still unknown. These results indicate that there are at least three intracellular messenger systems, protein kinase C, <Ca^(2+)> and cyclic AMP, which are involved in the growth factor-induced expression of the c-myc and c-fos genes in Swiss 3T3 cells. Another series of experiments have clarified that protein kinase C is involved in inhibition of the FGF-induced phospholipase C reaction and the <PGE_1> -induced <Ca^(2+)> influx in Swiss 3T3 cells. These observations together with the results described above suggest that protein kinase C acts as not only a positive but also a negative regulator for the growth factor-induced expression of the c-myc and c-fos genes in this cell line.
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