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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Adaptor Proteins, Vesicular Transport*
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Animals
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Environmental Pollutants
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GRB2 Adaptor Protein
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Liver / metabolism*
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Male
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Membrane Proteins / metabolism*
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Phosphotyrosine / metabolism
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Polychlorinated Dibenzodioxins / pharmacology*
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Protein Binding
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Protein-Tyrosine Kinases / metabolism
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Proteins / metabolism*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-cbl
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Rats
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Rats, Sprague-Dawley
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Shc Signaling Adaptor Proteins
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Signal Transduction
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Son of Sevenless Proteins
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Ubiquitin-Protein Ligases*
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Environmental Pollutants
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GRB2 Adaptor Protein
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Grb2 protein, rat
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Membrane Proteins
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Polychlorinated Dibenzodioxins
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Proteins
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Proto-Oncogene Proteins
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Shc Signaling Adaptor Proteins
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Shc1 protein, rat
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Son of Sevenless Proteins
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Phosphotyrosine
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Proto-Oncogene Proteins c-cbl
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Ubiquitin-Protein Ligases
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Protein-Tyrosine Kinases