Cloning of a novel receptor subunit, AcPL, required for interleukin-18 signaling
Cloning of a novel receptor subunit, AcPL, required for interleukin-18 signaling
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DOI：
10.1074/jbc.273.45.29445
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发表时间：
1998-11-06
影响因子：
4.8
通讯作者：
Sims, JE
中科院分区：
文献类型：
--
作者：
Born, TL;Thomassen, E;Sims, JE
我们已经确定了白细胞介素-1 （IL-1）受体家族的新成员，我们称之为AcPL。在瞬时转染实验中，我们无法证明AcPL在IL-1诱导的NF κ b活化中的作用，白细胞介素-18（干扰素- γ诱导因子）是IL-1细胞因子家族的另一个成员，最近有研究表明IL-18对IL-1R-rp1具有弱亲和力。我们研究了AcPL是否可能单独或与IL-1R-rp1协同作用来介导IL-18信号传导。我们发现IL-1R-rp1和AcPL的表达都是诱导NF κ B活性和c-Jun n末端激酶在IL-18反应中激活所必需的。此外，AcPL的显性阴性版本特异性抑制IL-18信号传导。体外免疫沉淀实验表明，单独的AcPL不能以任何明显的亲和力结合IL-18。我们提出，尽管IL-1R-rp1结合细胞因子，IL-1R-rp1和AcPL蛋白都是IL-18信号转导所必需的，类似于il -1介导的应答对IL-1R和IL-1RAcP的要求。
We have identified a novel member of the interleukin-1 (IL-1) receptor family, which we have termed AcPL. In transient transfection assays, we were unable to demonstrate a role for AcPL in IL-1-induced activation of NF kappa B. Interleukin-18 (interferon-gamma-inducing factor) is another member of the IL-1 family of cytokines, and it has recently been shown that IL-18 has a weak affinity for IL-1R-rp1. We examined whether AcPL might function alone or in concert with IL-1R-rp1 to mediate IL-18 signaling. We found that both IL-1R-rp1 and AcPL expression were required for induction of NF kappa B activity and for activation of c-Jun N-terminal kinase in response to IL-18. Furthermore, a dominant negative version of AcPL specifically inhibited IL-18 signaling. In vitro immunoprecipitation assays demonstrated that AcPL alone was unable to bind IL-18 with any appreciable affinity. We propose that although IL-1R-rp1 binds the cytokine, IL-1R-rp1 and AcPL proteins are both required for IL-18 signaling, analogous to the requirement for both IL-1R and IL-1RAcP in IL-1-mediated responses.