A conserved p38 mitogen-activated protein kinase pathway regulates Drosophila immunity gene expression
A conserved p38 mitogen-activated protein kinase pathway regulates Drosophila immunity gene expression
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DOI：
10.1128/mcb.18.6.3527
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发表时间：
1998-06-01
影响因子：
5.3
通讯作者：
Ip, YT
中科院分区：
文献类型：
--
作者：
Han, ZQS;Enslen, H;Ip, YT
越来越多的证据表明，昆虫和哺乳动物的先天性免疫应答是由同源调节成分介导的。促炎细胞因子和细菌脂多糖通过激活转录因子如NF-κ B和AP-1刺激哺乳动物免疫。由这些刺激引起的反应之一是激酶级联的启动，其导致位于亚结构域VIII内的基序Thr-Gly-Tyr内的Thr和Tyr上的p38促分裂原活化蛋白（MAP）激酶的磷酸化。我们研究了p38 MAP激酶通路在果蝇免疫应答中的可能参与。对与哺乳动物p38 MAP激酶高度同源的两个基因进行了分子克隆和表征。此外，还鉴定了编码两种新的果蝇MAP激酶激酶D-MKK 3和D-MKK 4的基因。D-MKK 3是果蝇p38 MAP激酶的有效激活剂，而D-MKK 4是D-JNK的激活剂，但不是D-p38的激活剂。这些数据证实果蝇确实具有保守的p38 MAP激酶信号通路。我们研究了D-p38 MAP激酶在昆虫免疫调节中的作用。结果表明，D-p38的功能之一是减弱抗菌肽基因表达后暴露于脂多糖。
Accumulating evidence suggests that the insect and mammalian innate immune response is mediated by homologous regulatory components. Proinflammatory cytokines and bacterial lipopolysaccharide stimulate mammalian immunity by activating transcription factors such as NF-kappa B and AP-1. One of the responses evoked by these stimuli is the initiation of a kinase cascade that leads to the phosphorylation of p38 mitogen-activated protein (MAP) kinase on Thr and Tyr within the motif Thr-Gly-Tyr, which is located within subdomain VIII. We have investigated the possible involvement of the p38 MAP kinase pathway in the Drosophila immune response. Two genes that are highly homologous to the mammalian p38 MAP kinase were molecularly cloned and characterized. Furthermore, genes that encode two novel Drosophila MAP kinase kinases, D-MKK3 and D-MKK4, were identified. D-MKK3 is an efficient activator of both Drosophila p38 MAP kinases, while D-MKK4 is an activator of D-JNK but not D-p38. These data establish that Drosophila indeed possesses a conserved p38 MAP kinase signaling pathway. We have examined the role of the D-p38 MAP kinases in the regulation of insect immunity. The results revealed that one of the functions of D-p38 is to attenuate antimicrobial peptide gene expression following exposure to lipopolysaccharide.