| Autor: |
VanArsdale TL; Division of Biomedical Sciences, University of California, Riverside 92521, USA., VanArsdale SL, Force WR, Walter BN, Mosialos G, Kieff E, Reed JC, Ware CF |
| Jazyk: |
angličtina |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 1997 Mar 18; Vol. 94 (6), pp. 2460-5. |
| DOI: |
10.1073/pnas.94.6.2460 |
| Abstrakt: |
The binding of heterotrimeric lymphotoxin, LT alpha1 beta2, to the LTbeta receptor (LTbeta R), a member of the tumor necrosis factor receptor (TNFR) superfamily, induces nuclear factor kappaB (NF-kappaB) activation and cell death in HT29 adenocarcinoma cells. We now show that treatment with LT alpha1 beta2 or agonistic LTbeta R antibodies causes rapid recruitment of TNFR-associated factor 3 (TRAF3) to the LTbeta R cytoplasmic domain. Further, stable overexpression of a TRAF3 mutant that lacks the RING and zinc finger domains inhibits LTbeta R-mediated cell death. The inhibition is specific for LTbeta R cell death signaling, since NF-kappaB activation by LT alpha1 beta2 and Fas-mediated apoptosis are not inhibited in the same cells. The mutant and endogenous TRAF3s are both recruited at equimolar amounts to the LTbeta R, suggesting that the mutant disrupts the function of the signaling complex. These results implicate TRAF3 as a critical component of the LTbeta R death signaling complex and indicate that at least two independent signaling pathways are initiated by LTbeta R ligation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
