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

38 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
Publication statusPublished - Feb 2 2004
Externally publishedYes

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Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Kettner, A., Kumar, L., Antón, I. M., Sasahara, Y., De La Fuente, M., Pivniouk, V. I., ... 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