Interaction of human MUC1 and beta-catenin is regulated by Lck and ZAP-70 in activated Jurkat T cells

Biochem Biophys Res Commun. 2004 Mar 5;315(2):471-6. doi: 10.1016/j.bbrc.2004.01.075.


The MUC1 transmembrane glycoprotein is aberrantly expressed by diverse hematologic malignancies, including those of the T cell lineage. The MUC1 cytoplasmic domain (CD) interacts with beta-catenin; however, the role of MUC1 in T cells is not known. In the present work, MUC1 was studied as a potential downstream effector of the Lck and ZAP-70 tyrosine kinases that are essential for T cell activation. The results demonstrate that anti-CD3-induced or PMA+ionomycin-induced activation of Jurkat T cells is associated with increased binding of MUC1 and Lck. Lck phosphorylates MUC1-CD on Y-46 and, in turn, stimulates the binding of MUC1 to beta-catenin. The results further demonstrate that MUC1 interacts with ZAP-70. In contrast to Lck, ZAP-70 phosphorylates MUC1-CD predominantly on Y-20. However, like Lck, ZAP-70-mediated phosphorylation of MUC1 Y-20 stimulates binding of MUC1 and beta-catenin. These findings indicate that MUC1 functions as a substrate for Lck and ZAP-70 in activated Jurkat T cells and that MUC1 integrates T cell receptor signaling with the beta-catenin pathway.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cell Division
  • Cell Line, Tumor
  • Cell Lineage
  • Cell Survival
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / metabolism*
  • Glutathione Transferase / metabolism
  • Humans
  • Ionomycin / pharmacology
  • Ionophores / pharmacology
  • Jurkat Cells
  • Lymphocyte Activation
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / physiology*
  • Molecular Sequence Data
  • Mucin-1 / chemistry
  • Mucin-1 / metabolism*
  • Phosphorylation
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / physiology*
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Time Factors
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism*
  • Tyrosine / metabolism
  • ZAP-70 Protein-Tyrosine Kinase
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Ionophores
  • Mucin-1
  • Recombinant Fusion Proteins
  • Trans-Activators
  • beta Catenin
  • Tyrosine
  • Ionomycin
  • Glutathione Transferase
  • Protein-Tyrosine Kinases
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human