IRAK-4 is a serine/threonine kinase that can bind to interleukin-1 receptor induced by interleukin-1. It plays a key role in the Toll-like receptor signaling pathway and is involved in innate and adaptive immune responses. In this study, piscine IRAK-4 significantly activated nuclear factor (NF)-κB signaling in grouper spleen cells. Grouper (Epinephelus coioides) IRAK-4 (EcIRAK-4) co-localized with EcMyD88 and did not impair EcMyD88-dependent NF-κB activation. Different doses of EcIRAK-4 caused different degrees of nuclear translocation of the transcription factor NF-κB p65 subunit, and it induced transcription of multiple pro-inflammatory cytokines. Using expression vectors of deletion domains or mutations at important sites of EcIRAK-4, we found that the EcIRAK-4 kinase domain is necessary for its signal transduction function. The conserved amino acid sites performed functions similar to those in mammals, and grouper-specific amino acids such as E339 also played important roles. These findings provide information about the functional characteristics of IRAK-4 in lower vertebrates.

IRAK-4是一种丝氨酸/苏氨酸激酶，可以与白介素1诱导的白介素1受体结合。它在Toll样受体信号传导途径中起关键作用，并参与先天性和适应性免疫反应。在这项研究中，鱼IRAK-4在石斑鱼脾脏细胞中显着激活了核因子（NF）-κB信号传导。石斑鱼（Epinephelus coioides）IRAK-4（Ec IRAK-4）与Ec MyD88共定位，并且不损害Ec MyD88依赖性的NF-κB活化。不同剂量的EcIRAK-4引起转录因子NF-κBp65亚基的不同程度的核易位，并诱导多种促炎细胞因子的转录。使用Ec IRAK-4重要部位缺失结构域或突变的表达载体，我们发现Ec IRAK-4激酶结构域是其信号转导功能所必需的。保守的氨基酸位点具有与哺乳动物相似的功能，石斑鱼特异性氨基酸如E339也起着重要的作用。这些发现提供了有关IRAK-4在低等脊椎动物中的功能特征的信息。