WIP Regulates Signaling via the High Affinity Receptor for Immunoglobulin E in Mast Cells

Wiskott-Aldrich syndrome protein–interacting protein (WIP) stabilizes actin filaments and is important for immunoreceptor-mediated signal transduction leading to actin cytoskeleton rearrangement in T and B cells. Here we report a role for WIP in signaling pathways downstream of the high affinity receptor for immunoglobulin (Ig)E (FcϵRI) in mast cells. WIP-deficient bone marrow–derived mast cells (BMMCs) were impaired in their capacity to degranulate and secrete interleukin 6 after FcϵRI ligation. Calcium mobilization, phosphorylation of Syk, phospholipase C-g2, and c-Jun NH₂-terminal kinase were markedly decreased in WIP-deficient BMMCs. WIP was found to associate with Syk after FcϵRI ligation and to inhibit Syk degradation as evidenced by markedly diminished Syk levels in WIP-deficient BMMCs. WIP-deficient BMMCs exhibited no apparent defect in their subcortical actin network and were normal in their ability to form protrusions when exposed to an IgE-coated surface. However, the kinetics of actin changes and the cell shape changes that follow FcϵRI signaling were altered in WIP-deficient BMMCs. These results suggest that WIP regulates FcϵRI-mediated mast cell activation by regulating Syk levels and actin cytoskeleton rearrangement.