Abstract
Wiskott-Aldrich syndrome protein (WASP) is the product of the gene deficient in boys with X-linked Wiskott-Aldrich syndrome. We assessed the role of WASP in signaling through the high-affinity IgE receptor (FcepsilonRI) using WASP-deficient mice. IgE-dependent degranulation and cytokine secretion were markedly diminished in bone marrow-derived mast cells from WASP-deficient mice. Upstream signaling events that include FcepsilonRI-triggered total protein tyrosine phosphorylation, and protein tyrosine phosphorylation of FcepsilonRIbeta and Syk were not affected by WASP deficiency. However, tyrosine phosphorylation of phospholipase Cgamma and Ca(2+) mobilization were diminished. IgE-dependent activation of c-Jun N-terminal kinase, cell spreading and redistribution of cellular F-actin in mast cells were reduced in the absence of WASP. We conclude that WASP regulates FcepsilonRI-mediated granule exocytosis, cytokine production and cytoskeletal changes in mast cells.
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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Actins / analysis
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Actins / metabolism
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Animals
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Blotting, Western
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / metabolism
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Calcium / metabolism
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Cell Degranulation / physiology
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Cell Differentiation / drug effects
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Cell Differentiation / genetics
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Cell Surface Extensions / drug effects
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Dinitrophenols / immunology
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Dinitrophenols / pharmacology
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Female
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Flow Cytometry
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Histamine / blood
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Immunization, Passive
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Immunoglobulin E / analysis
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Immunoglobulin E / immunology
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Immunoglobulin E / pharmacology
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Interleukin-3 / pharmacology
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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JNK Mitogen-Activated Protein Kinases
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Male
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Mast Cells / chemistry
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Mast Cells / physiology*
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Mice
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Mice, Knockout
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Microscopy, Fluorescence
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Mitogen-Activated Protein Kinases / metabolism
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Nerve Tissue Proteins / analysis
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Phospholipase C gamma
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Phosphorylation
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Protein Serine-Threonine Kinases / metabolism
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Protein-Tyrosine Kinases / metabolism
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Proteins / analysis
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Proteins / genetics
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Proteins / physiology*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Receptor Aggregation / immunology
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Receptors, IgE / metabolism
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Receptors, IgE / physiology*
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Serum Albumin / pharmacology
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Signal Transduction / physiology*
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Tumor Necrosis Factor-alpha / metabolism
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Type C Phospholipases / metabolism
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Wiskott-Aldrich Syndrome Protein
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Wiskott-Aldrich Syndrome Protein, Neuronal
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beta-N-Acetylhexosaminidases / metabolism
Substances
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Actins
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Dinitrophenols
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Interleukin-3
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Interleukin-6
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Nerve Tissue Proteins
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Proteins
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Proto-Oncogene Proteins
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Receptors, IgE
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Serum Albumin
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Tumor Necrosis Factor-alpha
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Was protein, mouse
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Wasl protein, mouse
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Wiskott-Aldrich Syndrome Protein
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Wiskott-Aldrich Syndrome Protein, Neuronal
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dinitrophenyl-human serum albumin conjugate
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Immunoglobulin E
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Histamine
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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Type C Phospholipases
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Phospholipase C gamma
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beta-N-Acetylhexosaminidases
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Calcium