Abstract：
The JAK-STAT pathway is a central communication node for various biological processes. Its activation is characterized by phosphorylation and nuclear translocation of the transcription factor STAT. The regulatory balance of JAK-STAT signaling is important for maintenance of immune homeostasis. Protein tyrosine phosphatases (PTPs) induce dephosphorylation of tyrosine residues in intracellular proteins and generally function as negative regulators in cell signaling. However, the roles of PTPs in JAK-STAT signaling, especially in invertebrates, remain largely unknown. Pacific white shrimp Penaeus vannamei is currently an important model for studying invertebrate immunity. This study identified a novel member of the dual-specificity phosphatase (DUSP) subclass of the PTP superfamily in P. vannamei, named PvDUSP14. By interacting with and dephosphorylating STAT, PvDUSP14 inhibits the excessive activation of the JAK-STAT pathway, and silencing of PvDUSP14 significantly enhances humoral and cellular immunity in shrimp. The promoter of PvDUSP14 contains a STAT-binding motif and can be directly activated by STAT, suggesting that PvDUSP14 is a regulatory target gene of the JAK-STAT pathway and mediates a negative feedback regulatory loop. This feedback loop plays a role in maintaining homeostasis of JAK-STAT signaling and is involved in antibacterial and antiviral immune responses in shrimp. Therefore, the current study revealed a novel inhibitory mechanism of JAK-STAT signaling, which is of significance for studying the regulatory mechanisms of immune homeostasis in invertebrates.
摘要：
JAK-STAT通路是各种生物过程的中心通信节点。其激活的特征在于转录因子STAT的磷酸化和核易位。JAK-STAT信号的调节平衡对于维持免疫稳态是重要的。蛋白质酪氨酸磷酸酶(PTP)诱导细胞内蛋白质中酪氨酸残基的去磷酸化,并且通常在细胞信号传导中充当负调节因子。然而,PTPs在JAK-STAT信号中的作用，尤其是在无脊椎动物中，基本上是未知的。太平洋白虾南美白对虾是目前研究无脊椎动物免疫的重要模型。这项研究确定了凡纳滨对虾PTP超家族的双特异性磷酸酶（DUSP）亚类的新成员，名为PvDUSP14。通过与STAT相互作用和去磷酸化，PvDUSP14抑制JAK-STAT通路的过度激活,沉默PvDUSP14能显著增强对虾的体液免疫和细胞免疫。PvDUSP14的启动子含有STAT结合基序，可以直接被STAT激活，提示PvDUSP14是JAK-STAT通路的调控靶基因，介导负反馈调控环。该反馈回路在维持JAK-STAT信号的稳态中起作用,并且参与虾的抗菌和抗病毒免疫应答。因此,目前的研究揭示了JAK-STAT信号的一种新的抑制机制，这对于研究无脊椎动物免疫稳态的调节机制具有重要意义。
