Protein kinase C delta regulates function of the DF3/MUC1 carcinoma antigen in beta-catenin signaling.
The DF3/MUC1 mucin-like glycoprotein is aberrantly overexpressed in most human carcinomas. The MUC1 cytoplasmic domain interacts directly with beta-catenin, a component of the adherens junction of mammalian epithelial cells. The present results demonstrate that MUC1 associates with protein kinase Cdelta (PKCdelta). A TDR sequence adjacent to the beta-catenin binding motif in the MUC1 cytoplasmic domain functions as a site for PKCdelta phosphorylation. We show that phosphorylation of MUC1 by PKCdelta increases binding of MUC1 and beta-catenin in vitro and in vivo. The functional significance of the MUC1-PKCdelta interaction is further supported by the demonstration that mutation of the PKCdelta phosphorylation site abrogates MUC1-mediated decreases in binding of beta-catenin to E-cadherin. We also show that the stimulatory effects of MUC1 on anchorage-independent growth are abrogated by mutation of the PKCdelta phosphorylation site. These findings support a novel role for PKCdelta in regulating the interaction between MUC1 and the beta-catenin signaling pathway.
Pubmed ID: 11877440 RIS Download
Amino Acid Sequence | Animals | Antigens, Neoplasm | Base Sequence | Cadherins | Cell Adhesion | Cytoskeletal Proteins | Electrophoresis, Polyacrylamide Gel | Female | Humans | Isoenzymes | Mice | Molecular Sequence Data | Phosphorylation | Protein Binding | Protein Kinase C | Protein Kinase C-delta | Trans-Activators | Tumor Cells, Cultured | beta Catenin