DF3/MUC1 signaling in multiple myeloma cells is regulated by interleukin-7

Cancer Biol Ther. Mar-Apr 2003;2(2):187-93. doi: 10.4161/cbt.2.2.282.

Abstract

The human DF3/MUC1 transmembrane protein is aberrantly expressed in multiple myeloma cells and other B cell malignancies. The regulation of MUC1 in B cells and its potential function as a signaling molecule are unknown. The present results demonstrate that interleukin-7 (IL-7) stimulates MUC1 expression in multiple myeloma cells. The results also demonstrate the IL-7 induces binding of MUC1 to the Lyn tyrosine kinase. The MUC1 C-terminal subunit binds directly to Lyn through interactions with the Lyn SH3 and SH2 domains. Activation of Lyn in response to IL-7 stimulation results in increased tyrosine phosphorylation of the MUC1 C-terminal subunit. In vitro and in vivo studies show that Lyn phosphorylates MUC1, at least in large part, on a YEKV site in the MUC1 cytoplasmic tail. The functional significance of the MUC1-Lyn interaction is supported by the demonstration that Lyn-mediated phosphorylation of MUC1 on YEKV induces binding of MUC1 and the beta-catenin signaling protein. In concert with these results, IL-7 treatment is associated with binding of MUC1 to beta-catenin and targeting of the MUC1-beta-catenin complex to the nucleus. These findings indicate that IL-7 regulates MUC1 expression and function in multiple myeloma cells.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cytoskeletal Proteins / metabolism
  • DNA Primers / chemistry
  • Fluorescent Antibody Technique
  • Humans
  • Immunoblotting
  • Interleukin-7 / pharmacology*
  • Molecular Sequence Data
  • Mucin-1 / biosynthesis*
  • Multiple Myeloma / metabolism*
  • Phosphorylation
  • Polymerase Chain Reaction
  • Precipitin Tests
  • Protein Binding
  • Recombinant Proteins
  • Signal Transduction
  • Trans-Activators / metabolism
  • Transfection
  • Tumor Cells, Cultured / drug effects
  • Tyrosine / metabolism
  • beta Catenin
  • src-Family Kinases / metabolism

Substances

  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA Primers
  • Interleukin-7
  • Mucin-1
  • Recombinant Proteins
  • Trans-Activators
  • beta Catenin
  • Tyrosine
  • lyn protein-tyrosine kinase
  • src-Family Kinases