Discs large (Dlg1) complexes in lymphocyte activation.
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.
Xavier
Ramnik
R
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Rabizadeh
Shahrooz
S
Ishiguro
Kazuhiro
K
Andre
Niko
N
Ortiz
J Bernabe
JB
Wachtel
Heather
H
Morris
David G
DG
Lopez-Ilasaca
Marco
M
Shaw
Albert C
AC
Swat
Wojciech
W
Seed
Brian
B
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017252:CD3 Complex / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D000074288:Discs Large Homolog 1 Protein; D051528:Guanylate Kinases; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D021381:Protein Transport; D011506:Proteins / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D018089:Superantigens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D017252:CD3 Complex; C513314:DLG1 protein, human; D004268:DNA-Binding Proteins; D000074288:Discs Large Homolog 1 Protein; C000614189:Dlg1 protein, mouse; C501119:Dlg1 protein, rat; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011506:Proteins; D018089:Superantigens; D014157:Transcription Factors; D051528:Guanylate Kinases