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Description
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A cDNA for a novel protein termed Tob (Transducer of ErbB-2) that interacts with the c-erbB-2 gene product p185erbB2 was molecularly cloned. Nucleotide sequencing reveals that the Tob protein is a 45 kDa protein that does not contain either SH2 or SH3 domain but is homologous to the previously characterized anti-proliferative gene product BTG-1 at its amino-terminal half. The carboxyl-terminal half of Tob is characterized by the presence of a sequence rich in proline and glutamine and shows no homology to known proteins. Like BTG-1, exogenously expressed Tob is able to suppress growth of NIH3T3 cells, but the growth suppression is hampered by the presence of kinase-active p185erbB2. By using the SGT-Tob protein that contains either full length or amino-terminal half of Tob, The carboxyl-terminal half of Tob is relevant to its interaction with p185erbB2. In addition, co-immunoprecipitation of the Tob protein with anti-ErbB-2 antibody and reciprocally the p185erbB2 with anti-Tob antibodies could be conducted. These data suggest that p185erbB2 negatively regulates the Tob-mediated anti-proliferative pathway through its interaction with Tob, requlsing possibly in growth stimulation by p185erbB2. The expression of the Tob mRNA is observed in various cell types and is not correlated with expression of c-erbB-2, suggesting that other receptor-type protein-tyrosine kinases are also involved the Tob-mediated regulation of cell growth.
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