The epidermal growth factor receptor regulates interaction of the human DF3/MUC1 carcinoma antigen with c-Src and beta-catenin.
J Biol Chem
; 276(38): 35239-42, 2001 Sep 21.
Article
in En
| MEDLINE
| ID: mdl-11483589
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Trans-Activators
/
Proto-Oncogene Proteins pp60(c-src)
/
Mucin-1
/
Cytoskeletal Proteins
/
ErbB Receptors
/
Antigens, Neoplasm
Limits:
Humans
Language:
En
Journal:
J Biol Chem
Year:
2001
Document type:
Article
Affiliation country:
United States