Abstract
Activation of the nuclear factor of activated T cells transcription factor (NF-AT) is a key event underlying lymphocyte action. The CAML (calcium-modulator and cyclophilin ligand) protein is a coinducer of NF-AT activation when overexpressed in Jurkat T cells. A member of the tumor necrosis factor receptor superfamily was isolated by virtue of its affinity for CAML. Cross-linking of this lymphocyte-specific protein, designated TACI (transmembrane activator and CAML-interactor), on the surface of transfected Jurkat cells with TACI-specific antibodies led to activation of the transcription factors NF-AT, AP-1, and NFkappaB. TACI-induced activation of NF-AT was specifically blocked by a dominant-negative CAML mutant, thus implicating CAML as a signaling intermediate.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Calcineurin
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Calmodulin-Binding Proteins / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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Cell Membrane / metabolism
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DNA-Binding Proteins / metabolism*
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Humans
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Jurkat Cells
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Lymphocyte Activation
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Membrane Proteins*
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Molecular Sequence Data
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Mutation
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NF-kappa B / metabolism
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NFATC Transcription Factors
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Nuclear Proteins*
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Phosphoprotein Phosphatases / metabolism
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Receptors, Tumor Necrosis Factor / chemistry
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / metabolism*
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Sequence Alignment
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Signal Transduction
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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Transcription Factor AP-1 / metabolism
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Transcription Factors / metabolism*
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Transcription, Genetic
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Transfection
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Transmembrane Activator and CAML Interactor Protein
Substances
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Adaptor Proteins, Signal Transducing
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CAMLG protein, human
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Calmodulin-Binding Proteins
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Carrier Proteins
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DNA-Binding Proteins
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Membrane Proteins
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NF-kappa B
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NFATC Transcription Factors
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Nuclear Proteins
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Receptors, Tumor Necrosis Factor
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TNFRSF13B protein, human
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Transcription Factor AP-1
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Transcription Factors
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Transmembrane Activator and CAML Interactor Protein
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Calcineurin
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Phosphoprotein Phosphatases