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

Yongqing Li, Jian Ren, Wei Hsuan Yu, Quan Li, Hiroaki Kuwahara, Li Yin, Kermit L Carraway, Donald Kufe

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210 Scopus citations


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 β-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 β-catenin. These findings support a novel role for EGF-R in regulating interactions of MUC1 with c-Src and β-catenin.

Original languageEnglish (US)
Pages (from-to)35239-35242
Number of pages4
JournalJournal of Biological Chemistry
Issue number38
StatePublished - Sep 21 2001


ASJC Scopus subject areas

  • Biochemistry

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