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The Wiskott-Aldrich syndrome protein regulates nuclear translocation of NFAT2 and NF-kappa B (RelA) independently of its role in filamentous actin polymerization and actin cytoskeletal rearrangement
Journal article   Peer reviewed

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

Winifred Huang, Hans D Ochs, Bo Dupont and Yatin M Vyas
The Journal of immunology (1950), Vol.174(5), pp.2602-2611
03/01/2005
DOI: 10.4049/jimmunol.174.5.2602
PMID: 15728466

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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-induced 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-kappaB (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-gamma1, in the disorganized NK cell immune synapse. Production of GM-CSF, but not IFN-gamma, 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.
 Cell Communication - immunology Natural Cytotoxicity Triggering Receptor 1 Receptors, Immunologic - physiology Membrane Microdomains - metabolism Humans Actins - metabolism Transcription Factor RelA Type C Phospholipases - metabolism NF-kappa B - metabolism Type C Phospholipases - antagonists & inhibitors Wiskott-Aldrich Syndrome - genetics DNA-Binding Proteins - metabolism Membrane Microdomains - immunology Signal Transduction - immunology Lymphocyte Activation - genetics Membrane Glycoproteins - physiology Cell Nucleus - metabolism Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis Phospholipase C gamma Killer Cells, Natural - immunology Clone Cells Active Transport, Cell Nucleus - genetics Wiskott-Aldrich Syndrome - metabolism Cytotoxicity, Immunologic - genetics Proteins - physiology Wiskott-Aldrich Syndrome - immunology Membrane Microdomains - enzymology Nuclear Proteins - metabolism Signal Transduction - genetics Cell Communication - genetics NFATC Transcription Factors Killer Cells, Natural - enzymology Proteins - genetics Transcription Factors - metabolism Wiskott-Aldrich Syndrome Protein Cytoskeleton - metabolism Granulocyte-Macrophage Colony-Stimulating Factor - antagonists & inhibitors Killer Cells, Natural - metabolism Cell Line, Transformed Interferon-gamma - biosynthesis

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