Abstract
CD43, the most abundant membrane protein of T lymphocytes, is able to initiate signals that lead to Ca2+ mobilization and interleukin-2 production, yet the molecular events involved in signal transduction pathway of the CD43 molecule are only beginning to be understood. We have shown recently that cross-linking CD43 on the cell surface of human T lymphocytes with the anti-CD43 monoclonal antibody L10 leads to CD43-Fyn kinase interactions and to Fyn phosphorylation on tyrosine residues. This interaction seems to be mediated by the SH3 domain of Fyn and a proline-rich sequence located in the cytoplasmic domain of CD43. Here we show that CD43-specific activation of human T lymphocytes induced tyrosine phosphorylation of the adaptor protein Shc and of the guanine exchange factor Vav, as well as the formation of a macromolecular complex that comprises Shc, GRB2, and Vav. CD43 ligation resulted in enhanced formation of Vav.SLP-76 complexes and in the activation and nuclear translocation of ERK2. Cross-linking of the CD43 molecule in 3T3-CD43(+) cells induced luciferase activity from a construct under the control of the Fos serum responsive element. Altogether, these data suggest that the mitogen-activated protein kinase pathway is involved in CD43-dependent interleukin-2 gene expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Adaptor Proteins, Signal Transducing*
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Adaptor Proteins, Vesicular Transport*
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Animals
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Antigens, CD*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Calcium-Calmodulin-Dependent Protein Kinases / physiology*
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Cross-Linking Reagents / metabolism
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GRB2 Adaptor Protein
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Gene Expression Regulation / genetics
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Genes, Reporter / genetics
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Genes, fos / genetics
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Humans
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Interleukin-2 / genetics
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Leukosialin
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Mice
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Mitogen-Activated Protein Kinase 1
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Oncogene Proteins / metabolism
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Phosphorylation
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Proteins / metabolism
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Proto-Oncogene Proteins c-vav
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Shc Signaling Adaptor Proteins
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Sialoglycoproteins / physiology*
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Signal Transduction / physiology
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Src Homology 2 Domain-Containing, Transforming Protein 1
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T-Lymphocytes / physiology*
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Transfection / genetics
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Tyrosine / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Antigens, CD
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Cross-Linking Reagents
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GRB2 Adaptor Protein
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GRB2 protein, human
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Grb2 protein, mouse
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Interleukin-2
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Leukosialin
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Oncogene Proteins
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Proteins
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Proto-Oncogene Proteins c-vav
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SHC1 protein, human
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SPN protein, human
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Shc Signaling Adaptor Proteins
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Shc1 protein, mouse
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Sialoglycoproteins
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Spn protein, mouse
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Src Homology 2 Domain-Containing, Transforming Protein 1
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VAV1 protein, human
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Vav1 protein, mouse
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Tyrosine
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1