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

Alexander Kettner, Lalit Kumar, Inés M. Antón, Yoji Sasahara, Miguel De La Fuente, Vadim I. Pivniouk, Hervé Falet, John H. Hartwig, Raif S. Geha

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

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 NH 2-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.

Original languageEnglish (US)
Pages (from-to)357-368
Number of pages12
JournalJournal of Experimental Medicine
Volume199
Issue number3
DOIs
StatePublished - Feb 2 2004

Keywords

  • Cytoskeleton
  • Signal transduction
  • WASP
  • WIP
  • Wiskott-Aldrich syndrome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kettner, A., Kumar, L., Antón, I. M., Sasahara, Y., De La Fuente, M., Pivniouk, V. I., Falet, H., Hartwig, J. H., & Geha, R. S. (2004). WIP Regulates Signaling via the High Affinity Receptor for Immunoglobulin E in Mast Cells. Journal of Experimental Medicine, 199(3), 357-368. https://doi.org/10.1084/jem.20030652