Abstract
Syk-family tyrosine kinases are essential for lymphocyte development and activation. Using a yeast two-hybrid screen to identify Syk kinases-interacting proteins (SKIPs), we isolated 3BP2, an Abl SH3-interacting protein of unknown function. 3BP2 was selectively expressed in hematopoietic/lymphoid tissues and bound via its SH2 domain activated Syk-family kinases in mammalian cells, including in antigen receptor-stimulated T cells. In addition to Zap-70, the 3BP2 SH2 domain associated in vitro with LAT, Grb2, PLCgamma1, and Cbl from activated T cell lysates. Transient 3BP2 overexpression induced transcriptional activation of the IL-2 promoter and its NFAT or AP-1 elements. This activity was dependent on the SH2 and pleckstrin-homology domains of 3BP2, and required functional Syk kinases, Ras, and calcineurin. Thus, 3BP2 is an important adaptor that may couple activated Zap-70/Syk to a LAT-containing signaling complex involved in TCR-mediated gene transcription.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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COS Cells
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DNA-Binding Proteins / physiology
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Enzyme Precursors / metabolism
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Enzyme Precursors / physiology*
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Gene Expression Regulation / physiology*
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Humans
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Interleukin-2 / biosynthesis*
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Interleukin-2 / genetics
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Intracellular Signaling Peptides and Proteins
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Jurkat Cells
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Lymphocyte Activation / physiology
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NFATC Transcription Factors
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Nuclear Proteins*
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Promoter Regions, Genetic / physiology
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Protein-Tyrosine Kinases / metabolism
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Protein-Tyrosine Kinases / physiology*
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Proto-Oncogene Proteins c-abl / isolation & purification
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Proto-Oncogene Proteins c-abl / metabolism
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Proto-Oncogene Proteins c-abl / physiology*
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Saccharomyces cerevisiae
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Signal Transduction / physiology
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Syk Kinase
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T-Lymphocytes / physiology
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Tissue Distribution
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Transcription Factor AP-1 / physiology
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Transcription Factors / physiology
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Transcriptional Activation
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ZAP-70 Protein-Tyrosine Kinase
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src Homology Domains / physiology
Substances
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DNA-Binding Proteins
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Enzyme Precursors
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Interleukin-2
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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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Transcription Factor AP-1
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Transcription Factors
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Protein-Tyrosine Kinases
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Proto-Oncogene Proteins c-abl
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SYK protein, human
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Syk Kinase
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ZAP-70 Protein-Tyrosine Kinase
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ZAP70 protein, human