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 Journal Article
| Authors: | Huang, W.; Ochs, H. D.; Dupont, B.; Vyas, Y. M. |
| Article Title: | 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 |
| 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. |
| Keywords: | signal transduction; clinical article; controlled study; unclassified drug; human cell; dna-binding proteins; protein function; proteins; immunoglobulin enhancer binding protein; protein interaction; transcription factor rela; cytotoxicity; transcription factors; nuclear proteins; cytokine; lymphocyte activation; transcription regulation; chemokine; protein synthesis; membrane glycoproteins; janus kinase; nf-kappa b; cell line, transformed; active transport, cell nucleus; natural killer cell; killer cells, natural; cytotoxicity, immunologic; cell nucleus; actins; cytokine release; cell interaction; cell communication; actin polymerization; cytoskeleton; clone cells; protein kinase zap 70; transcription factor nfat; phospholipase c gamma; receptors, immunologic; stat protein; granulocyte-macrophage colony-stimulating factor; calcium mobilization; membrane microdomains; wiskott aldrich syndrome protein; calcineurin; interferon type ii; nfatc transcription factors; phospholipase c gamma1; protein p46; transcription factor nfat2; phospholipase c; wiskott-aldrich syndrome; wiskott-aldrich syndrome protein |
| Journal Title: | Journal of Immunology |
| Volume: | 174 |
| Issue: | 5 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2005-03-01 |
| Start Page: | 2602 |
| End Page: | 2611 |
| Language: | English |
| PUBMED: | 15728466 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 31" - "Export Date: 24 October 2012" - "CODEN: JOIMA" - "Source: Scopus" |
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