Akiba H, Nakano H, Nishinaka S, Shindo M, Kobata T, Atsuta M, Morimoto C, Ware C F, Malinin N L, Wallach D, Yagita H, Okumura K
Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.
J Biol Chem. 1998 May 22;273(21):13353-8. doi: 10.1074/jbc.273.21.13353.
CD27 is a member of the tumor necrosis factor (TNF) receptor superfamily and is expressed on T, B, and NK cells. The signal via CD27 plays pivotal roles in T-T and T-B cell interactions. Here we demonstrate that overexpression of CD27 activates NF-kappaB and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK). Deletion analysis of the cytoplasmic domain of CD27 revealed that the C-terminal PIQEDYR motif was indispensable for both NF-kappaB and SAPK/JNK activation and was also required for the interaction with TNF receptor-associated factor (TRAF) 2 and TRAF5, both of which have been implicated in NF-kappaB activation by members of the TNF-R superfamily. Co-transfection of a dominant negative TRAF2 or TRAF5 blocked NF-kappaB and SAPK/JNK activation induced by CD27. Recently, a TRAF2-interacting kinase has been identified, termed NF-kappaB-inducing kinase (NIK). A kinase-inactive mutant NIK blocked CD27-, TRAF2-, and TRAF5-mediated NF-kappaB and SAPK/JNK activation. These results indicate that TRAF2 and TRAF5 are involved in NF-kappaB and SAPK/JNK activation by CD27, and NIK is a common downstream kinase of TRAF2 and TRAF5 for NF-kappaB and SAPK/JNK activation.
CD27是肿瘤坏死因子（TNF）受体超家族的成员，在T细胞、B细胞和NK细胞上表达。经由CD27的信号在T-T和T-B细胞相互作用中起关键作用。在此我们证明，CD27的过表达激活核因子κB（NF-κB）和应激激活蛋白激酶（SAPK）/c-Jun氨基末端激酶（JNK）。对CD27胞质结构域的缺失分析显示，C末端的PIQEDYR基序对于NF-κB和SAPK/JNK的激活都是必不可少的，并且也是与TNF受体相关因子（TRAF）2和TRAF5相互作用所必需的，这两者都与TNF-R超家族成员介导的NF-κB激活有关。共转染显性负性TRAF2或TRAF5可阻断CD27诱导的NF-κB和SAPK/JNK激活。最近，已鉴定出一种与TRAF2相互作用的激酶，称为NF-κB诱导激酶（NIK）。一种激酶失活的突变体NIK可阻断CD27、TRAF2和TRAF5介导的NF-κB和SAPK/JNK激活。这些结果表明，TRAF2和TRAF5参与了CD27介导的NF-κB和SAPK/JNK激活，并且NIK是TRAF2和TRAF5在NF-κB和SAPK/JNK激活过程中的共同下游激酶。
