title: The epidermal growth factor receptor regulates interaction of the human DF3/MUC1 carcinoma antigen with c-Src and beta-catenin.
abstract: 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.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Ren
authors.forename: W
authors.initials: W
authors.lastname: Yu
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Kuwahara
authors.forename: L
authors.initials: L
authors.lastname: Yin
authors.forename: K L
authors.initials: KL
authors.lastname: Carraway
authors.forename: D
authors.initials: D
authors.lastname: Kufe
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D018396:Mucin-1 / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin
chemical_list: D000951:Antigens, Neoplasm; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D018396:Mucin-1; D015534:Trans-Activators; D051176:beta Catenin; D066246:ErbB Receptors; D016392:Proto-Oncogene Proteins pp60(c-src)