Abstract
Crosslinking of multivalent antigen bound IgE transduces FcepsilonRI mediated signaling cascades, which activate nonreceptor-type protein-tyrosine kinases and subsequent tyrosine phosphorylation of cellular proteins, and these are critical elements for degranulation in mast cells. We cloned a novel adaptor molecule, signal transducing adaptor protein (STAP)-2 containing PH and SH2-like domains as a c-fms interacting protein. STAP-2 was identical to a recently cloned adaptor molecule, BKS, a substrate of BRK (breast tumor kinase) tyrosine kinase, although its function is still unknown. To examine a novel function of STAP-2/BSK, we expressed STAP-2/BSK or its mutants in rat basophilic leukemia RBL-2H3 cells. Overexpression of STAP-2/BSK resulted in a suppression of FcepsilonRI-mediated calcium mobilization and degranulation. FcepsilonRI-induced tyrosine phosphorylation of phospholipase C-gamma (PLC-gamma) but not Syk was significantly suppressed in these cells. Furthermore, STAP-2/BSK associated with PLC-gamma in vivo. These data indicate that STAP-2/BSK negatively controls the FcepsilonRI-mediated calcium mobilization and degranulation by direct modulation of tyrosine phosphorylation of PLC-gamma.
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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Adaptor Proteins, Vesicular Transport / genetics
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Adaptor Proteins, Vesicular Transport / metabolism*
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Animals
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Calcium / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Enzyme Precursors / metabolism
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Genes, Reporter
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Humans
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Intracellular Signaling Peptides and Proteins
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Leukemia, Basophilic, Acute
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Mast Cells / cytology
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Mast Cells / metabolism
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NFATC Transcription Factors
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Nuclear Proteins*
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Phospholipase C gamma
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Phosphoproteins*
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Protein-Tyrosine Kinases / metabolism
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Rats
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Receptors, IgE / genetics
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Receptors, IgE / metabolism*
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / immunology*
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Signal Transduction / physiology
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Syk Kinase
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Tumor Cells, Cultured
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Type C Phospholipases / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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DNA-Binding Proteins
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Enzyme Precursors
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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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Phosphoproteins
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Receptors, IgE
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Recombinant Fusion Proteins
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STAP2 protein, human
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Transcription Factors
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Protein-Tyrosine Kinases
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SYK protein, human
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Syk Kinase
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Syk protein, rat
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Type C Phospholipases
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Phospholipase C gamma
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Calcium