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

• DOI: 10.1074/jbc.c100359200
• Publication Date: 2002-07-26T15:08:15Z
• Authors: Quan Li; Hiroaki Kuwahara; Li Yin; Yongqing Li; Jian Ren; Wei-hsuan Yu; Kermit L. Carraway; Donald Kufe
• Keywords: Mucin-1; Proto-Oncogene Proteins pp60(c-src); 3. Good health; ErbB Receptors; Cytoskeletal Proteins; 03 medical and health sciences; 0302 clinical medicine; Microscopy, Fluorescence; Antigens, Neoplasm; Trans-Activators; Tumor Cells, Cultured; Humans; Phosphorylation; beta Catenin; Protein Binding

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.