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. doi: 10.1074/jbc.M200436200. Epub 2002 Mar 4.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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

Substances

  • 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