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 (FceRI) 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 FceRI-triggered total protein tyrosine phosphorylation, and protein tyrosine phosphorylation of FceRIβ 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 FceRI-mediated granule exocytosis, cytokine production and cytoskeletal changes in mast cells.