Protein kinase C delta regulates function of the DF3/MUC1 carcinoma antigen in beta-catenin signaling.
Article Details
- CitationCopy to clipboard
Ren J, Li Y, Kufe D
Protein kinase C delta regulates function of the DF3/MUC1 carcinoma antigen in beta-catenin signaling.
J Biol Chem. 2002 May 17;277(20):17616-22. Epub 2002 Mar 4.
- PubMed ID
- 11877440 [ View in PubMed]
- Abstract
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.