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

Abstract:

:c-Src kinases and p21 Ras are known to be implicated in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated signal transduction. However, the effects of TCDD on the molecular interaction of adaptor complex in the protein tyrosine kinase signaling cascade have not been reported. The present study is designed to clarify whether TCDD modulates the molecular interactions of Shc, Cbl, Grb2, and Sos in primary rat hepatocytes. TCDD causes an electrophoretic mobility shift of Sos and increases Sos/Grb2 association. Tyrosine phosphorylated Shc, mainly p52, unloads to the Grb2/Sos complex upon TCDD stimulation. Interestingly, TCDD decreases the tyrosine phosphorylation level of Cbl, although Cbl recruits more Grb2 and Shc proteins by TCDD. These results indicate that TCDD modulates the molecular interaction of adaptor complex proteins including Shc, Grb2, Sos, and Cbl. Furthermore, tyrosine phosphorylation of Cbl may not be critical for interaction of the protein with Grb2 and Shc in the TCDD signaling pathway in primary rat hepatocytes.

authors

Park R,Kim DH,Kim MS,So HS,Chung HT,Kwon KB,Ryu DG,Kim BR

doi

10.1006/bbrc.1998.9816

subject

Has Abstract

pub_date

1998-12-30 00:00:00

pages

577-81

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(98)99816-3

journal_volume

253

pub_type

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