期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：17
页码：9803-9808
DOI：10.1073/pnas.96.17.9803
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：TRAF5 [tumor necrosis factor (TNF) receptor-associated factor 5] is implicated in NF-{kappa}B and c-Jun NH2-terminal kinase/stress-activated protein kinase activation by members of the TNF receptor superfamily, including CD27, CD30, CD40, and lymphotoxin-{beta} receptor. To investigate the functional role of TRAF5 in vivo, we generated TRAF5-deficient mice by gene targeting. Activation of either NF-{kappa}B or c-Jun NH2-terminal kinase/stress-activated protein kinase by tumor necrosis factor, CD27, and CD40 was not abrogated in traf5-/- mice. However, traf5-/- B cells showed defects in proliferation and up-regulation of various surface molecules, including CD23, CD54, CD80, CD86, and Fas in response to CD40 stimulation. Moreover, in vitro Ig production of traf5-/- B cells stimulated with anti-CD40 plus IL-4 was reduced substantially. CD27-mediated costimulatory signal also was impaired in traf5-/- T cells. Collectively, these results demonstrate that TRAF5 is involved in CD40- and CD27-mediated signaling.
