TANK potentiates tumor necrosis factor receptor-associated factor-mediated c-Jun N-terminal kinase/stress-activated protein kinase activation through the germinal center kinase pathway.
TANK potentiates tumor necrosis factor receptor-associated factor-mediated c-Jun N-terminal kinase/stress-activated protein kinase activation through the germinal center kinase pathway.
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TANK 通过生发中心激酶途径增强肿瘤坏死因子受体相关因子介导的 c-Jun N 末端激酶/应激激活蛋白激酶的激活。
DOI：
10.1128/mcb.19.10.6665
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发表时间：
1999
影响因子：
5.3
通讯作者：
Cheng,G
中科院分区：
文献类型：
--
作者：
Chin,AI;Shu,J;ShanShi,C;Yao,Z;Kehrl,JH;Cheng,G
肿瘤坏死因子（TNF）受体相关因子（TRAFs）是TNF受体超家族许多成员的介质，并且可以激活核因子κB（NF-κB）和应激活化蛋白激酶（SAPK;也称为c-Jun N-末端激酶）信号转导途径。我们先前描述了TRAF相互作用分子TRAF相关NF-κB激活剂（TANK）参与TRAF 2介导的NF-κB激活。在这里，我们表明，TANK与TRAF 2，TRAF 5和TRAF 6协同作用，但不与TRAF 3在SAPK激活。TRAF 2和TANK分别与生发中心激酶（GCK）相关激酶（GCKR）形成弱相互作用。然而，当共表达时，它们与GCKR形成强复合物，从而为TRAF和TANK在GCKR介导的SAPK活化中的协同作用提供了潜在机制，这在TNF家族受体信号传导中很重要。我们的研究结果还表明，TANK可以形成潜在的分子间以及分子内的相互作用之间的氨基端和羧基端。这项研究表明，TANK是一种调节分子，控制TNF受体激活后NF-κB和SAPK活性的阈值。此外，CD 40激活了原代B细胞中的内源性GCKR，暗示GCK家族蛋白参与了CD 40介导的B细胞功能。
Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are mediators of many members of the TNF receptor superfamily and can activate both the nuclear factor κB (NF-κB) and stress-activated protein kinase (SAPK; also known as c-Jun N-terminal kinase) signal transduction pathways. We previously described the involvement of a TRAF-interacting molecule, TRAF-associated NF-κB activator (TANK), in TRAF2-mediated NF-κB activation. Here we show that TANK synergized with TRAF2, TRAF5, and TRAF6 but not with TRAF3 in SAPK activation. TRAF2 and TANK individually formed weak interactions with germinal center kinase (GCK)-related kinase (GCKR). However, when coexpressed, they formed a strong complex with GCKR, thereby providing a potential mechanism for TRAF and TANK synergy in GCKR-mediated SAPK activation, which is important in TNF family receptor signaling. Our results also suggest that TANK can form potential intermolecular as well as intramolecular interactions between its amino terminus and carboxyl terminus. This study suggests that TANK is a regulatory molecule controlling the threshold of NF-κB and SAPK activities in response to activation of TNF receptors. In addition, CD40 activated endogenous GCKR in primary B cells, implicating GCK family proteins in CD40-mediated B-cell functions.