Protein kinase C delta regulates function of the DF3/MUC1 carcinoma antigen in beta-catenin signaling.

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.
Authors	Jian Ren, Yongqing Li, Donald Kufe
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 277 Issue 20 Pg. 17616-22 (May 17 2002) ISSN: 0021-9258 [Print] United States
PMID	11877440 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Antigens, Neoplasm CTNNB1 protein, human CTNNB1 protein, mouse Cadherins Cytoskeletal Proteins Isoenzymes Trans-Activators beta Catenin Prkcd protein, mouse PRKCD protein, human Protein Kinase C Protein Kinase C-delta
Topics	Amino Acid Sequence Animals Antigens, Neoplasm (physiology) Base Sequence Cadherins (metabolism) Cell Adhesion Cytoskeletal Proteins (physiology) Electrophoresis, Polyacrylamide Gel Female Humans Isoenzymes (physiology) Mice Molecular Sequence Data Phosphorylation Protein Binding Protein Kinase C (physiology) Protein Kinase C-delta Trans-Activators Tumor Cells, Cultured beta Catenin

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