Association of the DF3/MUC1 breast cancer antigen with Grb2 and the Sos/Ras exchange protein.
The DF3/MUC1 mucin-like glycoprotein is aberrantly overexpressed in human breast carcinomas. Although the precise functional role of this protein remains unclear, the cytoplasmic tail contains potential tyrosine phosphorylation sites for binding to Src homology 2 (SH2) domains. In the present studies using human MCF-7 breast cancer cells, we show that tyrosine phosphorylated DF3 directly interacts with the SH2 domain of the adaptor protein Grb2. The findings indicate that a pYTNP site in DF3 is responsible for this interaction. The results also demonstrate that the DF3/Grb2 complex associates with the guanine nucleotide exchange protein Sos. Because Sos binds to the SH3 domains of Grb2 and, thereby, associates with Ras at the cell membrane, formation of a DF3/Grb2/Sos complex supports a role for DF3 in intracellular signaling.
Pandey
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Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kharbanda
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Kufe
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D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D051380:GRB2 Adaptor Protein; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D020663:ras Guanine Nucleotide Exchange Factors
D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins; D020663:ras Guanine Nucleotide Exchange Factors