The mitogen-activated protein kinome from Anopheles gambiae: identification, phylogeny and functional characterization of the ERK, JNK and p38 MAP kinases.
The mitogen-activated protein kinome from Anopheles gambiae: identification, phylogeny and functional characterization of the ERK, JNK and p38 MAP kinases.
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DOI：
10.1186/1471-2164-12-574
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发表时间：
2011-11-23
期刊：
影响因子：
4.4
通讯作者：
Luckhart S
中科院分区：
文献类型：
--
作者：
Horton AA;Wang B;Camp L;Price MS;Arshi A;Nagy M;Nadler SA;Faeder JR;Luckhart S
冈比亚按蚊是撒哈拉以南非洲地区人类疟疾寄生虫的主要蚊媒。迄今为止，三种先天性免疫信号传导途径，包括核因子（NF）-κ B依赖性Toll和免疫缺陷（IMD）途径和Janus激酶/信号转导和转录激活因子（Jak-STAT）途径，已在An.冈比亚。然而，除了NF-κ B依赖的信号传导外，JNK、ERK和p38 MAPK调节的三种丝裂原活化蛋白激酶（MAPK）途径是其他无脊椎动物和哺乳动物先天免疫的关键介质。我们对MAPK信号级联在按蚊先天免疫中的作用的理解是有限的，因此需要鉴定这些蛋白质的编码补体、其上游激活剂和响应相关免疫信号的磷酸化谱。在本研究中，我们介绍了17个An的直系同源物和同源性。冈比亚MAPKs，其中两个是以前未知的，另外两个是不完全注释。我们还提供了详细的时间激活ERK，JNK，和p38 MAPK在AN。冈比亚细胞在体外对与疟疾寄生虫感染（人胰岛素、人转化生长因子-β 1、过氧化氢）和细菌脂多糖相关的免疫信号的反应。这些激活配置文件和可能的上游调控途径解释在已知的MAPK信号级联。基于最先进的蚊子基因组注释建立MAPK“路线图”可以加速我们对宿主-病原体相互作用和更广泛的An生理学的理解。冈比亚和其他蚊子物种。此外，未来的努力，以开发按蚊细胞信号传导反应的预测模型，基于迭代的建设和完善的数据为基础的和基于文献的知识的MAP激酶级联和其他网络化的途径，将有助于识别的“主信号调节器”在生物医学上重要的蚊子物种。
Anopheles gambiae is the primary mosquito vector of human malaria parasites in sub-Saharan Africa. To date, three innate immune signaling pathways, including the nuclear factor (NF)-kappaB-dependent Toll and immune deficient (IMD) pathways and the Janus kinase/signal transducers and activators of transcription (Jak-STAT) pathway, have been extensively characterized in An. gambiae. However, in addition to NF-kappaB-dependent signaling, three mitogen-activated protein kinase (MAPK) pathways regulated by JNK, ERK and p38 MAPK are critical mediators of innate immunity in other invertebrates and in mammals. Our understanding of the roles of the MAPK signaling cascades in anopheline innate immunity is limited, so identification of the encoded complement of these proteins, their upstream activators, and phosphorylation profiles in response to relevant immune signals was warranted. In this study, we present the orthologs and phylogeny of 17 An. gambiae MAPKs, two of which were previously unknown and two others that were incompletely annotated. We also provide detailed temporal activation profiles for ERK, JNK, and p38 MAPK in An. gambiae cells in vitro to immune signals that are relevant to malaria parasite infection (human insulin, human transforming growth factor-beta1, hydrogen peroxide) and to bacterial lipopolysaccharide. These activation profiles and possible upstream regulatory pathways are interpreted in light of known MAPK signaling cascades. The establishment of a MAPK "road map" based on the most advanced mosquito genome annotation can accelerate our understanding of host-pathogen interactions and broader physiology of An. gambiae and other mosquito species. Further, future efforts to develop predictive models of anopheline cell signaling responses, based on iterative construction and refinement of data-based and literature-based knowledge of the MAP kinase cascades and other networked pathways will facilitate identification of the "master signaling regulators" in biomedically important mosquito species.
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