Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, China.
Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, China.
J Immunol. 2021 Dec 15;207(12):3060-3069. doi: 10.4049/jimmunol.2100486. Epub 2021 Nov 19.
The Stat signaling pathway plays important roles in mediating the secretions of a large number of cytokines and growth factors in vertebrates, which is generally triggered by the growth factor receptor, cytokine receptor, G protein coupled receptor, and receptor protein tyrosine kinase. In the current study, a platelet-derived growth factor receptor (defined as PDGFRβ) was identified from the Pacific oyster , with a signal peptide, three Ig domains, a transmembrane domain, and an intracellular Ser/Thr/Tyr kinase domain. The two N-terminal Ig domains of PDGFRβ showed relatively higher binding activity to Gram-negative bacteria and LPS compared with Gram-positive bacteria and peptidoglycan. Upon binding bacteria, PDGFRβ in hemocytes formed a dimer and interacted with protein tyrosine kinase Src to induce the phosphorylation of Src at Tyr416. The activated Src interacted with Stat to induce the translocation of Stat into the nucleus of hemocytes, which then promoted the expressions of Big defensin 1 (Bigdef1), IL17-4 (IL17-4), and TNF (TNF1). These findings together demonstrated that the Src/Stat signaling was activated after the binding of PDGFRβ with bacteria to induce the expressions of Bigdef1, IL17-4, and TNF1.
Stat 信号通路在脊椎动物中大量细胞因子和生长因子的分泌中发挥重要作用，通常由生长因子受体、细胞因子受体、G 蛋白偶联受体和受体蛋白酪氨酸激酶触发。在本研究中，从太平洋牡蛎中鉴定出一种血小板衍生生长因子受体（定义为 PDGFRβ），其具有信号肽、三个 Ig 结构域、跨膜结构域和细胞内 Ser/Thr/Tyr 激酶结构域。PDGFRβ 的两个 N 端 Ig 结构域与革兰氏阴性菌和 LPS 的结合活性相对较高，而与革兰氏阳性菌和肽聚糖的结合活性较低。当与细菌结合时，血细胞中的 PDGFRβ 形成二聚体并与蛋白酪氨酸激酶 Src 相互作用，诱导 Src 在 Tyr416 处磷酸化。激活的 Src 与 Stat 相互作用，诱导 Stat 向血细胞核内易位，从而促进 Big defensin 1（Bigdef1）、IL17-4（IL17-4）和 TNF（TNF1）的表达。这些发现共同表明，PDGFRβ 与细菌结合后，Src/Stat 信号被激活，诱导 Bigdef1、IL17-4 和 TNF1 的表达。
