• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

Authors

  • Ren J
  • Li Y
  • Kufe D

Journal

The Journal of biological chemistry

Publication Data

May 17, 2002

Associated Grants

  • Agency: NCI NIH HHS, Id: CA87421

Mesh Terms

  • 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