Abstract
The widely expressed transmembrane molecule CD46 is the complement regulatory receptor for C3b as well as the receptor for several pathogens. Beside its binding functions, CD46 is also able to transduce signals. We showed that CD46 aggregation on human T cells induces p120CBL and linker for activation of T cells (LAT) phosphorylation. These two proteins are adaptor proteins known to regulate TCR signaling. p120CBL is a complex adaptor protein involved in negatively regulating signaling events, whereas LAT is a transmembrane adaptor protein found in glycolipid-enriched microdomains essential for T cell activation. Therefore, we investigated if a CD46/TCR costimulation would affect T cell activation. Indeed, CD46/CD3 costimulation strongly promotes T cell proliferation. Therefore, we propose that CD46 acts as a potent costimulatory molecule for human T cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Antigens, CD / physiology*
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CD3 Complex / physiology
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Carrier Proteins / metabolism*
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Cell Line
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Humans
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Intracellular Fluid / metabolism
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Lymphocyte Activation / immunology
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Membrane Cofactor Protein
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Membrane Glycoproteins / physiology*
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Membrane Proteins*
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Phosphoproteins / metabolism*
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Phosphorylation
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-cbl
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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Tyrosine / metabolism
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Ubiquitin-Protein Ligases*
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, CD
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CD3 Complex
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CD46 protein, human
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Carrier Proteins
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LAT protein, human
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Membrane Cofactor Protein
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Membrane Glycoproteins
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Membrane Proteins
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Phosphoproteins
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Proto-Oncogene Proteins
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Tyrosine
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Proto-Oncogene Proteins c-cbl
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Ubiquitin-Protein Ligases
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CBL protein, human