Association of Shc, Cbl, Grb2, and Sos following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin in primary rat hepatocytes

c-Src kinases and p21 Ras are known to be implicated in 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD)-mediated signal transduction. However, the effects of TCDD on the molecular interaction of adaptor complex in the protein tyro sine kinase signaling cascade have not been reported. The present study is designed to clarify whether TCDD modulates the molecular interactions of Sh c, Cbl, Grb2, and Sos in primary rat hepatocytes. TCDD causes an electropho retic mobility shift of Sos and increases Sos/Grba association. Tyrosine ph osphorylated Shc, mainly p52, unloads to the Grb2/Sos complex upon TCDD sti mulation. Interestingly, TCDD decreases the tyrosine phosphorylation level of Cbl, although Cbl recruits more Grb2 and Shc proteins by TCDD. These res ults indicate that TCDD modulates the molecular interaction of adaptor comp lex proteins including Shc, Grb2, Sos, and Chi. Furthermore, tyrosine phosp horylation of Cbl may not be critical for interaction of the protein with G rb2 and Shc in the TCDD signaling pathway in primary rat hepatocytes. (C) 1 998 Academic Press.