Abstract
Although numerous reports document a role for CD43 in T cell signaling, the direct participation of this molecule in cell activation has been questioned. In this study we show that CD43 ligation on human normal peripheral T cells was sufficient to induce interleukin-2, CD69, and CD40-L gene expression, without requiring signals provided by additional receptor molecules. This response was partially inhibited by cyclosporin A and staurosporine, suggesting the participation of both the Ca(2+) and the protein kinase C pathways in CD43 signaling. Consistent with the transient CD43-dependent intracellular Ca(2+) peaks reported by others, signals generated through the CD43 molecule resulted in the induction of NF-AT DNA binding activity. CD43-dependent signals resulted also in AP-1 and NFkappaB activation, probably as a result of protein kinase C involvement. AP-1 complexes bound to the AP-1 sequence contained c-Jun, and those bound to the NF-AT-AP-1 composite site contained c-Jun and Fos. NFkappaB complexes containing p65 could be found as early as 1 h after CD43 cross-linking, suggesting that CD43 participates in early events of T cell activation. The induction of the interleukin-2, CD69, and CD-40L genes and the participation of AP-1, NF-AT, and NFkappaB in the CD43-mediated signaling cascade implicate an important role for this molecule in the regulation of gene expression and cell function.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / metabolism
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Antigens, Differentiation, T-Lymphocyte / metabolism
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CD40 Ligand / metabolism
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Calcineurin Inhibitors
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Calcium / metabolism
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Calcium-Binding Proteins*
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Cell Nucleus / metabolism
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Cross-Linking Reagents / pharmacology
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Cyclosporine / pharmacology
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DNA / metabolism*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation
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Humans
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Interleukin-2 / metabolism
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Ions
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Jurkat Cells
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Lectins, C-Type
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Leukosialin
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Lymphocyte Activation
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Membrane Glycoproteins / metabolism
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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NFATC Transcription Factors
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Nerve Tissue Proteins / metabolism
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Nuclear Proteins*
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Promoter Regions, Genetic
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Protein Binding
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism
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Proto-Oncogene Proteins c-fos / metabolism
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Proto-Oncogene Proteins c-jun / metabolism
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sialoglycoproteins / metabolism*
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Signal Transduction
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Staurosporine / pharmacology
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Synaptotagmin I
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Synaptotagmins
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T-Lymphocytes / metabolism
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Time Factors
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Transcription Factor AP-1 / genetics
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Transcription Factor AP-1 / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD69 antigen
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Calcineurin Inhibitors
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Calcium-Binding Proteins
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Cross-Linking Reagents
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DNA-Binding Proteins
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Enzyme Inhibitors
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Interleukin-2
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Ions
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Lectins, C-Type
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Leukosialin
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Membrane Glycoproteins
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NF-kappa B
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NFATC Transcription Factors
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Nerve Tissue Proteins
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Nuclear Proteins
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Proto-Oncogene Proteins c-fos
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Proto-Oncogene Proteins c-jun
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RNA, Messenger
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SPN protein, human
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Sialoglycoproteins
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Synaptotagmin I
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Transcription Factor AP-1
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Transcription Factors
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Synaptotagmins
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CD40 Ligand
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Cyclosporine
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DNA
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Protein Kinase C
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Staurosporine
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Calcium