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Mechanisms of signaling from cell surface receptors to nuclear genes.

Research Project

Project/Area Number 60480496
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 物質生物化学
Research InstitutionKobe University

Principal Investigator

TAKAI Yoshimi  Kobe University, Faculty of Medicine, Professor, 医学部, 教授 (60093514)

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)
Project Period (FY) 1985 – 1986
Project Status Completed (Fiscal Year 1986)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1986: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1985: ¥4,100,000 (Direct Cost: ¥4,100,000)
KeywordsCell Surface Receptors / Nuclear Genes / Intracellular Messengers / Cyclic AMP / Calcium Ion / Protein Kinases / 細胞増殖因子
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.

Report

(1 results)
  • 1986 Final Research Report Summary
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Kaibuchi,K.: J.Biol.Chem.260. 1366-1369 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tsuda,T.: FEBS Lett.187. 43-46 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tsuda,T.: FEBS Lett.191. 205-210 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Sano,K.: FEBS Lett.192. 4-8 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Takeyama,Y.: FEBS Lett.193. 153-158 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Takai,Y.: J.Cell.Biochem.29. 143-155 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Kaibuchi,K.: J.Biol.Chem.261. 1187-1192 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Kikuchi,A.: J.Biol.Chem.261. 211558-1156 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yamashita,T.: J.Biol.Chem.261. 16878-16882 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Takeyama,Y: J.Clin.Invest.78. 1604-1611 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Hoshijima,M.: Cancer Res.46. 3000-3004 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Kikuchi,A.: Cancer Res.46. 3401-3406 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tsuda,T.: J.Biochem.100. 1631-1635 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Takeyama,Y.: FEBS Lett.197. 339-343 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tsuda,T.: FEBS Lett.208. 39-42 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Katakami,Y.: Biochem.Biophys.Res.Commun.135. 355-362 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Kawahara,Y: Throm.Res.41. 811-818 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Takai,Y.: In Gumma Symposia on Endocrinology,Molecular Mechanism of Biosignal Trasduction. 23. 69-84 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Kariya,K.: Atherosclerosis. (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yamashita,T.: J.Biol.Chem.(1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Kozo Kaibuchi: "Protein kinase C and calcium ion in mitogenic response of macrophage-depleted human peripheral lymphocytes." J. Biol. Chem.260. 1366-1369 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Terutaka Tsuda: "Involvement of calcium ion in platelet-derived growth factor-induced expression of c-myc oncogene in Swiss 3T3 fibroblasts." FEBS Lett.187. 43-46 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Terutaka Tsuda: "Induction of protein kinase C activation and <Ca^(2+)> mobilization by fibroblast growth factor in Swiss 3T3 cells." FEBS Lett.191. 205-210 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Kimihiko Sano: "Comparison of the modes of action of <Ca^(2+)> ionophore A23187 and thrombin in protein kinase C activation in human platelets." FEBS Lett.192. 4-8 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yoshifumi Takeyama: "Enhancement of growth factor-induced DNA synthesis by colon tumor-promoting bile acids in Swiss 3T3 cells: Their different mode of action from that of phorbol esters." FEBS Lett.193. 153-158 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yoshimi Takai: "Role of protein kinase C in transmembrane signaling." J. Cell. Biochem.29. 143-155 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Kozo Kaibuchi: "Possible involvement of protein kinase C and calcium ion in growth factor-induced expression of c-myc oncogene in Swiss 3T3 fibroblasts." J. Biol. Chem.261. 1187-1192 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Akira Kikuchi: "Direct evidence for involvement of a guanine nucleotide-binding protein in chemotactic peptide-stimulated formation of inositol bis- and trisphosphate in differentiated human leukemic (HL-60) cells: Reconstitution with Gi or <G_o> of the plasma membranes ADP-ribosylated by pertussis toxin." J. Biol. Chem.261. 11558-11562 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Takayuki Yamashita: "Possible involvement of cyclic AMP and calcium ion in prostaglandin <E_1> -induced elevation of c-myc mRNA in Swiss 3T3 fibroblasts." J. Biol. Chem.261. 16878-16882 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yoshifumi Takeyama: "Enhancement of secretagogue-induced phosphoinositide turnover and amylase secretion by bile acids in isolated rat pancreatic acini." J. Clin. Invest.78. 1604-1611 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Masahiko Hoshijima: "Formation of a phorbol ester-binding fragment from protein kinase C by proteolytic digestion." Cancer Res.46. 3000-3004 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Akira Kikuchi: "Inhibition of chemotactic peptide-induced phosphoinositide hydrolysis by phorbol esters through the activation of protein kinase C in differentiated human leukemia (HL-60) cells." Cancer Res.46. 3401-3406 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Terutaka Tsuda: "Epidermal growth factor increases c-myc mRNA without eliciting phosphoinositide turnover, protein kinase C activation or calcium ion mobilization in Swiss 3T3 fibroblasts." J. Biochem.100. 1631-1635 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yoshifumi Takeyama: "Enhancement of fibroblast growth factor-induced diacylglycerol formation and protein kinase C activation by colon tumor-promoting bile acid in Swiss 3T3 cells: Different modes of action between bile acid and phorbol ester." FEBS Lett.197. 339-343 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Terutaka Tsuda: "Involvement of three intracellular messenger systems, protein kinase C, calcium ion and cyclic AMP, in the regulation of c-fos gene expression in Swiss 3T3 cells." FEBS Lett.208. 39-42 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yuko Katakami: "Possible involvement of protein kinase C in interleukin-1 production by mouse peritoneal macrophages." Biochem. Biophys. Res. Commun.135. 355-362 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yasuhiro Kawahara: "Activation of protein kinase C by the action of 9,11-epithio-11,12-methano-thromboxane <A_2> ( <STA_2> ), a stable analogue of thromboxane <A_2> , in human platelets." Throm. Res.41. 811-818 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yoshimi Takai: "Protein kinase C and transmembrane signaling of growth factors in Swiss 3T3 fibroblasts." In Gumma Symposia on Endocrinology, Molecular Mechanism of Biosignal Transduction. 23. 69-84 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Ken-ichi Kariya: "Possible involvement of protein kinase C in platelet-derived growth factor-stimulated DNA synthesis in vascular smooth muscle cells." Atherosclerosis. in press (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Takayuki Yamashita: "Inhibition of prostaglandin <E_1> -induced elevation of cytoplasmic free calcium ion by protein kinase C-activating phorbol esters and diacylglycerol in Swiss 3T3 fibroblasts." J. Biol. Chem.in press (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary

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Published: 1987-03-31   Modified: 2016-04-21  

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