The Wiskott-Aldrich syndrome protein regulates nuclear translocation of NFAT2 and NF-κB (RelA) independently of its role in filamentous actin polymerization and actin cytoskeletal rearrangement

Winifred Huang, Hans D. Ochs, Bo Dupont, Yatin M. Vyas

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Effector functions mediated by NK cells involve cytotoxicity and transcription-dependent production and release of cytokines and chemokines. Although the JAK/STAT pathway mediates lymphokine-incluced transcriptional regulation in NK cells, very little is known about transcriptional regulation induced during cell-cell contact. We demonstrate that the Wiskott-Aldrich syndrome protein (WASp) is an important component for integration of signals leading to nuclear translocation of NFAT2 and NF-κB (RelA) during cell-cell contact and NKp46-dependent signaling. This WASp function is independent of its known role in F-actin polymerization and cytoskeletal rearrangement. Absence of WASp results in decreased accumulation of calcineurin, WASp-interacting protein, and molecules upstream of calcium mobilization, i.e., activated ZAP70 and phospholipase C-γ1, in the disorganized NK cell immune synapse. Production of GM-CSF, but not IFN-γ, is decreased, while natural cytotoxicity of Wiskott-Aldrich syndrome-NK cells is maintained. Our results indicate that WASp independently regulates its dual functions, i.e., actin cytoskeletal remodeling and transcription in NK cells.

Original languageEnglish (US)
Pages (from-to)2602-2611
Number of pages10
JournalJournal of Immunology
Volume174
Issue number5
DOIs
StatePublished - Mar 1 2005

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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