Faculty Collaboration Database

Impaired signaling via the high-affinity IgE receptor in Wiskott-Aldrich syndrome protein-deficient mast cells. Int Immunol 2003 Dec;15(12):1431-40

Date

12/03/2003

Pubmed ID

14645152

DOI

10.1093/intimm/dxg148

Scopus ID

2-s2.0-0347407821 (requires institutional sign-in at Scopus site)   39 Citations

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.

Author List

Pivniouk VI, Snapper SB, Kettner A, Alenius H, Laouini D, Falet H, Hartwig J, Alt FW, Geha RS

Author

Herve Falet PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Actins
Animals
Blotting, Western
Bone Marrow Cells
Calcium
Cell Degranulation
Cell Differentiation
Cell Surface Extensions
Dinitrophenols
Female
Flow Cytometry
Histamine
Immunization, Passive
Immunoglobulin E
Interleukin-3
Interleukin-6
JNK Mitogen-Activated Protein Kinases
Male
Mast Cells
Mice
Mice, Knockout
Microscopy, Fluorescence
Mitogen-Activated Protein Kinases
Nerve Tissue Proteins
Phospholipase C gamma
Phosphorylation
Protein-Tyrosine Kinases
Proteins
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-akt
Receptor Aggregation
Receptors, IgE
Serum Albumin
Signal Transduction
Tumor Necrosis Factor-alpha
Type C Phospholipases
Wiskott-Aldrich Syndrome Protein
Wiskott-Aldrich Syndrome Protein, Neuronal
beta-N-Acetylhexosaminidases