Essential function for the kinase TAK1 in innate and adaptive immune responses
Essential function for the kinase TAK1 in innate and adaptive immune responses
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DOI：
10.1038/ni1255
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发表时间：
2005-11-01
影响因子：
30.5
通讯作者：
Akira, S
中科院分区：
文献类型：
--
作者：
Sato, S;Sanjo, H;Akira, S
转化生长因子β激活激酶1（TAK 1）与白细胞介素1受体和肿瘤坏死因子受体信号转导有关。在这里，我们产生的小鼠品系与条件表达的Map 3 k7等位基因编码的一部分TAK 1。TAK 1缺陷的胚胎成纤维细胞表现出对白细胞介素1 β和肿瘤坏死因子的反应丧失。对具有B细胞特异性TAK 1缺陷的小鼠的研究表明，TAK 1对于对Toll样受体配体、CD 40和B细胞受体交联的细胞应答是不可或缺的。此外，抗原诱导的免疫应答在B细胞特异性TAK 1缺陷的小鼠中显著受损。TAK 1缺陷细胞不能激活转录因子NF-κ B和丝裂原活化蛋白激酶，以响应白细胞介素1 β、肿瘤坏死因子和Toll样受体配体。然而，TAK 1缺陷型B细胞能够激活NF-κ B B，但不能激活JNK激酶以响应B细胞受体刺激。这些结果共同表明，TAK 1是细胞对各种刺激反应的关键。
Transforming growth factor-beta-activated kinase 1 (TAK1) has been linked to interleukin 1 receptor and tumor necrosis factor receptor signaling. Here we generated mouse strains with conditional expression of a Map3k7 allele encoding part of TAK1. TAK1-deficient embryonic fibroblasts demonstrated loss of responses to interleukin 1 beta and tumor necrosis factor. Studies of mice with B cell-specific TAK1 deficiency showed that TAK1 was indispensable for cellular responses to Toll-like receptor ligands, CD40 and B cell receptor crosslinking. In addition, antigen-induced immune responses were considerably impaired in mice with B cell-specific TAK1 deficiency. TAK1-deficient cells failed to activate transcription factor NF-kappa B and mitogen-activated protein kinases in response to interleukin 1 beta, tumor necrosis factor and Toll-like receptor ligands. However, TAK1-deficient B cells were able to activate NF-kappa B but not the kinase Jnk in response to B cell receptor stimulation. These results collectively indicate that TAK1 is key in the cellular response to a variety of stimuli.