The Epidermal Growth Factor Receptor Regulates Interaction of the Human DF3/MUC1 Carcinoma Antigen with c-Src and β-Catenin

作者：Quan Li, Hiroaki Kuwahara, Li Yin, Yongqing Li, Jian Ren, Wei‐Hsuan Yu, Kermit L. Carraway, Donald W. Kufe · 发表于：Journal of Biological Chemistry · 年份：2001 · DOI：10.1074/jbc.c100359200 · 被引用次数：257 · 研究领域：HER2/EGFR in Cancer Research、Glycosylation and Glycoproteins Research、Monoclonal and Polyclonal Antibodies Research

The DF3/MUC1 mucin-like, transmembrane glycoprotein is aberrantly overexpressed in most human carcinomas. The MUC1 cytoplasmic domain interacts with the c-Src tyrosine kinase and thereby increases binding of MUC1 and beta-catenin. In the present work, coimmunoprecipitation studies demonstrate that MUC1 associates constitutively with the epidermal growth factor receptor (EGF-R) in human ZR-75-1 breast carcinoma cells. Immunofluorescence studies show that EGF-R and MUC1 associate at the cell membrane. We also show that the activated EGF-R phosphorylates the MUC1 cytoplasmic tail on tyrosine at a YEKV motif that functions as a binding site for the c-Src SH2 domain. The results demonstrate that EGF-R-mediated phosphorylation of MUC1 induces binding of MUC1 to c-Src in cells. Moreover, in vitro and in vivo studies demonstrate that EGF-R increases binding of MUC1 and beta-catenin. These findings support a novel role for EGF-R in regulating interactions of MUC1 with c-Src and beta-catenin.