Abstract
Two molecules involved in signal transduction via the T cell antigen receptor, namely the protein-tyrosine kinase ZAP-70 and the proto-oncoprotein Vav, were found to be constitutively associated with tubulin in Jurkat T cells. Both were able to bind to tubulin independently of one another, as determined by transient transfection into COS-7 cells. The ZAP-70 associated with tubulin was preferentially tyrosine-phosphorylated after T cell antigen receptor stimulation of Jurkat T cells, suggesting that this interaction was functionally significant. Vav was also found to co-immunoprecipitate with ZAP-70 from cell extracts depleted of tubulin. This raised the possibility that Vav might be a substrate for ZAP-70 protein-tyrosine kinase activity. However, tyrosine phosphorylation of Vav preceded that of ZAP-70, indicating that Vav was unlikely to be a downstream target of ZAP-70. The association of ZAP-70 and Vav with tubulin implies that the microtubules may be involved in the signaling function of these two molecules, perhaps by targeting them to their appropriate intracellular location.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Cycle Proteins*
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Cell Line
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Chlorocebus aethiops
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Cloning, Molecular
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Cytosol / metabolism
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Humans
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Immunosuppressive Agents / pharmacology
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Muromonab-CD3 / pharmacology
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Phosphorylation
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Phosphotyrosine / metabolism
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Protein-Tyrosine Kinases / isolation & purification
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Protein-Tyrosine Kinases / metabolism*
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Proto-Oncogene Proteins / isolation & purification
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-vav
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Receptors, Antigen, T-Cell / isolation & purification
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Receptors, Antigen, T-Cell / metabolism
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / metabolism
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T-Lymphocytes
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Transfection
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Tubulin / isolation & purification
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Tubulin / metabolism*
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Tumor Cells, Cultured
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ZAP-70 Protein-Tyrosine Kinase
Substances
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Cell Cycle Proteins
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Immunosuppressive Agents
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Muromonab-CD3
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-vav
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Receptors, Antigen, T-Cell
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Recombinant Proteins
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Tubulin
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VAV1 protein, human
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Phosphotyrosine
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Protein-Tyrosine Kinases
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ZAP-70 Protein-Tyrosine Kinase
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ZAP70 protein, human