A Role for Wiskott-Aldrich Syndrome Protein in T-cell Receptor-mediated Transcriptional Activation Independent of Actin Polymerization

Christopher Silvin, Barbara Belisle, Arie Abo
2001 Journal of Biological Chemistry  
Wiskott-Aldrich syndrome protein (WASP) plays a key role in cytoskeletal rearrangement and transcriptional activation in T-cells. Recent evidence links WASP and related proteins to actin polymerization by the Arp2/3 complex. To study whether the role of WASP in actin polymerization is coupled to T-cell receptor (TCR)-mediated transcriptional activation, we made a series of WASP deletion mutants and tested them for actin colocalization, actin polymerization, and transcriptional activation of
more » ... . A WASP mutant with a deletion in the C-terminal region (WASP⌬C) that is defective in actin polymerization potentiated NFAT transcription following TCR activation by anti-CD3 and anti-CD3/CD28 antibodies, but not by phorbol 12-myristate 13-acetate/ ionomycin. Furthermore, cotransfection of a dominantactive mutant (WASP-WH2-C) for Arp2/3 polymerization did not inhibit NFAT activation. Finally, by analyzing a series of WASP double-domain deletion mutants, we determined that the WASP homology-1 domain is responsible for NFAT transcriptional activation. Our results suggest that WASP activates transcription following TCR stimulation in a manner that is independent of its role in Arp2/3-directed actin polymerization.
doi:10.1074/jbc.m010729200 pmid:11283014 fatcat:qwilz7zignbc3iv3wgrxgalrkq