Nore1B regulates TCR signaling via Ras and Carma1.
Nore1A was originally identified as a potential Ras effector, and Nore1B is an alternatively spliced isoform. Both share a Ras/Rap association domain (RA domain) but only Nore1A contains sequence motifs that predict SH3 domain binding and diacylglycerol/phorbol ester binding in the amino-terminal region. Here we report that Carma1 binds to Nore1A and Nore1B through the RA domain and that Carma1 interacts with active Ras in the presence of Nore1B. RNA interference against Nore1B attenuates NF-kappaB activation induced by T cell receptor (TCR) ligation, but not NF-kappaB activation induced by TNFalpha or lipoteichoic acid. In addition, Nore1B is also required for KiRas GV12-mediated ERK1 activation and Elk1 reporter activity in T cells. We also provide evidence that knockdown of Nore1B also impairs polarized redistribution of Ras at the B cell-T cell immune interface. Together, these findings suggest that endogenous Nore1B recruits active Ras to the APC-T cell interface and mediates the interaction between Ras and Carma1.
Ishiguro
Kazuhiro
K
Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Avruch
Joe
J
Landry
Aimee
A
Qin
Shan
S
Ando
Takafumi
T
Goto
Hidemi
H
Xavier
Ramnik
R
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D053468:CARD Signaling Adaptor Proteins; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D016328:NF-kappa B; C454042:RASSF5 protein, human; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell; D050807:ets-Domain Protein Elk-1; D048052:Mitogen-Activated Protein Kinase 3; D020559:Monomeric GTP-Binding Proteins; D016283:Proto-Oncogene Proteins p21(ras); C426242:CARD11 protein, human; D006162:Guanylate Cyclase