Abstract
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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Cell Division
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Cell Line, Tumor
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Cell Lineage
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Cell Survival
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Cytoplasm / metabolism
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Cytoskeletal Proteins / chemistry
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Cytoskeletal Proteins / metabolism*
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Glutathione Transferase / metabolism
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Humans
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Ionomycin / pharmacology
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Ionophores / pharmacology
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Jurkat Cells
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Lymphocyte Activation
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / physiology*
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Molecular Sequence Data
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Mucin-1 / chemistry
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Mucin-1 / metabolism*
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Phosphorylation
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Precipitin Tests
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Protein Binding
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Protein Structure, Tertiary
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Protein-Tyrosine Kinases / physiology*
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Recombinant Fusion Proteins / metabolism
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Sequence Homology, Amino Acid
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Signal Transduction
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Time Factors
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Trans-Activators / chemistry
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Trans-Activators / metabolism*
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Tyrosine / metabolism
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ZAP-70 Protein-Tyrosine Kinase
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beta Catenin
Substances
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CTNNB1 protein, human
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Cytoskeletal Proteins
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Ionophores
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Mucin-1
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Recombinant Fusion Proteins
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Trans-Activators
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beta Catenin
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Tyrosine
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Ionomycin
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Glutathione Transferase
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Protein-Tyrosine Kinases
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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ZAP-70 Protein-Tyrosine Kinase
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ZAP70 protein, human