Association of the DF3/MUC1 Breast Cancer Antigen with Grb2 and the Sos/Ras Exchange Protein1

The DF3/MUC1 mucin-like glycoprotein is aberrantly overexpressed in human hreast carcinomas. Although the precise functional role of this protein remains unclear, the cytoplasmic tail contains potential l\ rosine phosphorylation sites for binding to Src homology 2 (SH2) domains. In the present studies using human \KT-7 breast cancer cells, we show that l\ rosine phosphorylated DP~3 directly interacts with the SH2 domain of the adaptor protein ( ,rl>2. The findings indicate that a pYTNP site in DF3 is responsible for this interaction. The results also demonstrate that the I)F3/Grb2 complex associates with the guanine nucleotide exchange pro tein Sos. Because Sos binds to the SH3 domains of Grb2 and, thereby, associates with Kas at the cell membrane, formation of a DK3/Grb2/Sos complex supports a role for DF3 in intracellular signaling.