Abstract
Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP), specifically binds to a region of WASp that is frequently mutated in Wiskott-Aldrich syndrome. Due to the similar phenotypes of WASp- and Vav-deficient T cells, and the putative importance of the WIP/WASp complex in mediating normal signals from the TCR, we investigated the role of WIP in regulating NF-AT/AP-1-mediated gene transcription. We show that WIP has the ability to enhance Vav-mediated activation of NF-AT/AP-1 gene transcription. In addition, we provide evidence that the interaction of WIP with WASp is necessary, but not sufficient for the ability of WIP to regulate NF-AT/AP-1 activity. Finally, we have identified a region in WIP required for its regulation of NF-AT/AP-1 activity. Our data suggests that the WIP-WASp interaction is important for NF-AT/AP-1-mediated gene transcription, and that defects seen in the activation of T cells from WAS patients may be due to the inability of these cells to form a functional WIP/WASp-signaling complex.
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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Biopolymers / physiology
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Carrier Proteins / physiology*
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Cell Cycle Proteins*
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Cytoskeletal Proteins
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DNA Mutational Analysis
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology
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Drug Synergism
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Humans
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Intracellular Signaling Peptides and Proteins
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Jurkat Cells
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Lymphocyte Activation / immunology*
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NFATC Transcription Factors
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Nuclear Proteins*
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Protein Binding / genetics
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Protein Binding / immunology
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Proteins / metabolism*
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-vav
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Sequence Deletion
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T-Lymphocytes / immunology*
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Transcription Factor AP-1 / metabolism
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Transcription Factor AP-1 / physiology
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Transcription Factors / metabolism
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Transcription Factors / physiology
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Transcription, Genetic / immunology
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Wiskott-Aldrich Syndrome / immunology
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Wiskott-Aldrich Syndrome / metabolism
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Wiskott-Aldrich Syndrome Protein
Substances
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Biopolymers
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Carrier Proteins
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Cell Cycle Proteins
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Intracellular Signaling Peptides and Proteins
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NFATC Transcription Factors
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Nuclear Proteins
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Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-vav
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Transcription Factor AP-1
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Transcription Factors
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VAV1 protein, human
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WAS protein, human
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WIPF1 protein, human
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Wiskott-Aldrich Syndrome Protein