Impaired signaling via the high‐affinity IgE receptor in Wiskott–Aldrich syndrome protein‐deficient mast cells

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 (FcϵRI) 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 FcϵRI‐triggered total protein tyrosine phosphorylation, and protein tyrosine phosphorylation of FcϵRIβ and Syk were not affected by WASP deficiency. However, tyrosine phosphorylation of phospholipase Cγ and Ca2+ 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 FcϵRI‐mediated granule exocytosis, cytokine production and cytoskeletal changes in mast cells.