Shi C S, Leonardi A, Kyriakis J, Siebenlist U, Kehrl J H
B Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Disease, Bethesda, MD 20892, USA.
J Immunol. 1999 Sep 15;163(6):3279-85.
TNF-induced activation of stress activated protein kinases (SAPKs, Jun NH2-terminal kinases) requires TNF receptor associated factor 2 (TRAF2). TRAF2 is a potent activator of a 95-kDa serine/threonine kinase termed germinal center kinase related (GCKR, also referred to as KHS1), which signals activation of the SAPK pathway. Consistent with a role for GCKR in TNF- induced SAPK activation, a kinase-inactive mutant of GCKR is a dominant negative inhibitor of TRAF2-induced SAPK activation. Here we show that TRAF2 interacts with GCKR. This interaction depended upon the TRAF domain of TRAF2 and the C-terminal 150 aa of GCKR. The full activation of GCKR by TRAF2 required the TRAF2 RING finger domain. TNF treatment of a T cell line, Jurkat, increased both GCRK and SAPK activity and enhanced the coimmunoprecipitation of GCKR with TRAF2. Similar results were found with the B cell line HS-Sultan. These findings are consistent with a model whereby TNF signaling results in the recruitment and activation of GCKR by TRAF2, which leads to SAPK activation.
肿瘤坏死因子（TNF）诱导应激激活蛋白激酶（SAPKs，即Jun氨基末端激酶）的激活需要肿瘤坏死因子受体相关因子2（TRAF2）。TRAF2是一种名为生发中心激酶相关蛋白（GCKR，也称为KHS1）的95 kDa丝氨酸/苏氨酸激酶的强效激活剂，它可发出信号激活SAPK途径。与GCKR在TNF诱导的SAPK激活中所起的作用一致，GCKR的激酶失活突变体是TRAF2诱导的SAPK激活的显性负性抑制剂。在此我们表明TRAF2与GCKR相互作用。这种相互作用依赖于TRAF2的TRAF结构域和GCKR的C末端150个氨基酸。TRAF2对GCKR的完全激活需要TRAF2的RING指结构域。用TNF处理T细胞系Jurkat，可增加GCRK和SAPK的活性，并增强GCKR与TRAF2的共免疫沉淀。在B细胞系HS-Sultan中也发现了类似结果。这些发现与一种模型一致，即TNF信号传导导致TRAF2募集并激活GCKR，进而导致SAPK激活。
