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.
SciCrunch is a data sharing and display platform. Anyone can create a custom portal where they can select searchable subsets of hundreds of data sources, brand their web pages and create their community. SciCrunch will push data updates automatically to all portals on a weekly basis. User communities can also add their own data to scicrunch, however this is not currently a free service.