Key Laboratory of Mariculture (Ocean University of China), Ministry of Education (KLMME), Ocean University of China, Qingdao, China.
Key Laboratory of Mariculture (Ocean University of China), Ministry of Education (KLMME), Ocean University of China, Qingdao, China.
Fish Shellfish Immunol. 2022 Feb;121:1-11. doi: 10.1016/j.fsi.2021.12.049. Epub 2021 Dec 31.
Mitogen-activated protein kinase kinases (MKKs) are intermediate kinases of mitogen-activated protein kinases (MAPKs) signaling pathways. MKKs are activated by mitogen-activated protein kinase kinase kinase (MKKK) and then the activated MKKs trigger the activation of downstream MAPKs. MAPK signaling pathways play an important role in regulating immune functions including apoptosis and inflammation. However, studies on identification and characterization of mkk repertoire in rainbow trout (Oncorhynchus mykiss) are still limited. Trout experienced 4 rounds (4R) of whole genome duplication (WGD), thus exhibiting increased paralogs of mkks with potentially functional diversity. In this study, we identified 17 mkk genes in trout and the following bacterial challenge (Vibrio anguillarum) studies showed functional diversity of different mkk subtypes. Vibrio anguillarum infection resulted in significantly up-regulated mkk2 subtypes in spleen and liver, and mkk4b3 in spleen, suggesting immunomodulation was regulated by activation of ERK, p38 and JNK pathways. Compared to other mkk subtypes, mkk6s were down-regulated in symptomatic group, rather than asymptomatic group. The organisms present negative feedback on MAPK activation, thus reducing extra damage to cells. We observed down-regulated mkk6s with up-regulated genes (dusp1 & dusp2) involved in negative feedback of MAPK activation. Based on these results, we might propose the distinct expression patterns of genes associated with MAPK pathways resulted in different phenotypes and symptoms of trout in response to bacterial challenge.
丝裂原活化蛋白激酶激酶(MKKs)是丝裂原活化蛋白激酶(MAPKs)信号通路的中间激酶。MKKs 被丝裂原活化蛋白激酶激酶激酶(MKKK)激活,然后激活的 MKKs 触发下游 MAPKs 的激活。MAPK 信号通路在调节免疫功能方面发挥着重要作用,包括细胞凋亡和炎症。然而,虹鳟(Oncorhynchus mykiss)中 mkk 基因库的鉴定和特征研究仍然有限。虹鳟经历了 4 轮全基因组复制(4R),因此具有潜在功能多样性的 MKKK 基因的基因倍增。在这项研究中,我们在虹鳟中鉴定了 17 个 mkk 基因,随后的细菌攻毒(鳗弧菌)研究表明不同 mkk 亚型具有功能多样性。鳗弧菌感染导致脾脏和肝脏中 mkk2 亚型和脾脏中 mkk4b3 显著上调,表明 ERK、p38 和 JNK 通路的激活调节了免疫调节。与其他 mkk 亚型相比,mkk6s 在有症状组中下调,而在无症状组中没有下调。机体对 MAPK 激活呈负反馈,从而减少对细胞的额外损伤。我们观察到 mkk6s 下调与 MAPK 激活负反馈相关的上调基因(dusp1 和 dusp2)。基于这些结果,我们可以提出与 MAPK 通路相关的基因的不同表达模式导致了虹鳟对细菌攻毒的不同表型和症状。