TY - JOUR
T1 - Targeted disruption of Traf5 gene causes defects in CD40- and CD27- mediated lymphocyte activation
AU - Nakano, H.
AU - Sakon, S.
AU - Koseki, H.
AU - Takemori, T.
AU - Tada, K.
AU - Matsumoto, M.
AU - Munechika, E.
AU - Sakai, T.
AU - Shirasawa, T.
AU - Akiba, H.
AU - Kobata, T.
AU - Santee, S. M.
AU - Ware, C. F.
AU - Rennert, P. D.
AU - Taniguchi, M.
AU - Yagita, H.
AU - Okumura, K.
PY - 1999/8/17
Y1 - 1999/8/17
N2 - TRAF5 [tumor necrosis factor (TNF) receptor-associated factor 5] is implicated in NF-κB and c-Jun NH2-terminal kinase/stress-activated protein kinase activation by members of the TNF receptor superfamily, including CD27, CD30, CD40, and lymphotoxin-β receptor. To investigate the functional role of TRAF5 in vivo, we generated TRAF5-deficient mice by gene targeting. Activation of either NF-κB 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 signalling.
AB - TRAF5 [tumor necrosis factor (TNF) receptor-associated factor 5] is implicated in NF-κB and c-Jun NH2-terminal kinase/stress-activated protein kinase activation by members of the TNF receptor superfamily, including CD27, CD30, CD40, and lymphotoxin-β receptor. To investigate the functional role of TRAF5 in vivo, we generated TRAF5-deficient mice by gene targeting. Activation of either NF-κB 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 signalling.
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U2 - 10.1073/pnas.96.17.9803
DO - 10.1073/pnas.96.17.9803
M3 - Article
C2 - 10449775
AN - SCOPUS:0033578329
VL - 96
SP - 9803
EP - 9808
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 17
ER -