Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin Induces Recruitment of Shc/Cbl/Grb2/Sos Conplex in Early Signaling Pathway of CYP1A1 Induction in the Primary Culture of Hepatocytes

  • Kim, Bok-Ryang (Department of Biochemistry) ;
  • Park, Rae-Kil (Department of Microbiology Wonkwang University) ;
  • Kim, Dong-Hyun (Bioanalysis Biotransformation Reserach Center , Korea Institute of Science and Technology)
  • Published : 1999.03.01
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Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) is known to induce cytochrome p450 1A1 and to activate c-Src kinase and p21 Ras. This study examined the molecular interactions of adaptor proteins including Shc, Grb2, and Sos in rat primary hepatocytes and their relationship to the induction of CYP1A1 by TCDD. TCDD induced CYP1A1 level and EROD activity in a dose-dependent mode. Sos/Grb2 association isincreased by TCDDㅑㅜ a dose dependent mode. Tyrosine phosphorylated Shc, mainly p152, onloads to Grb2/Sos complex upon TCDD stimulation. The electrophoretic mobility shift of Sos is showed by TCDD. These results indicate that TCDD modulated the molecular interaction features of adaptor compoes proteins including Shc, Grb2, and Cnl in early signaling pathway of TCDD-mediated CYP 1A1 induction of rat primary hepatocyte.

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References

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