Disc large (Dlg1) complexes in lymphocyte activation

Ramnik Xavier, Shahrooz Rabizadeh, Kazuhiro Ishiguro, Niko Andre, J. Bernabe Ortiz, Heather Wachtel, David G. Morris, Marco Lopez-Ilasaca, Albert C. Shaw, Wojciech Swat, Brian Seed

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82 Scopus citations

Abstract

T cell antigen recognition involves the formation of a structured interface between antigen-presenting and T cells that facilitates the specific transmission of activating and desensitizing stimuli. The molecular machinery that organizes the signaling molecules and controls their disposition in response to activation remains poorly understood. We show here that in T cells Discs large (Dlg1), a PDZ domain-containing protein, is recruited upon activation to cortical actin and forms complexes with early participants in T cell activation. Transient overexpression of Dlg1 attenuates basal and Vav1-induced NFAT reporter activation. Reduction of Dlg1 expression by RNA interference enhances both CD3- and superantigen-mediated NFAT activation. Attenuation of antigen receptor signaling appears to be a complex, highly orchestrated event that involves the mutual segregation of important elements of the early signaling complex.

Original languageEnglish
Pages (from-to)173-178
Number of pages6
JournalJournal of Cell Biology
Volume166
Issue number2
DOIs
StatePublished - Jul 19 2004

Keywords

  • Discs large
  • Lymphocyte activation
  • PDZ domains
  • Scaffold protein

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    Xavier, R., Rabizadeh, S., Ishiguro, K., Andre, N., Ortiz, J. B., Wachtel, H., Morris, D. G., Lopez-Ilasaca, M., Shaw, A. C., Swat, W., & Seed, B. (2004). Disc large (Dlg1) complexes in lymphocyte activation. Journal of Cell Biology, 166(2), 173-178. https://doi.org/10.1083/jcb.200309044