The phosphatidylinositol 3-kinase (PI3K) gene family plays a crucial role in key biological processes such as cell signal transduction, inflammatory response, metabolism and cell movement. Although its function in mammals, especially the mutation association in cancer, has been widely studied, the immune function of this family in teleosts, particularly the important economic fish species large yellow croaker, remains unclear. This study systematically identified 18 pi3k genes in the genome of large yellow croaker. Phylogenetic analysis indicated that this family had a high degree of evolutionary conservation among teleosts. Expression analyses revealed that multiple pi3k genes exhibited significant changes in expression levels under conditions of infection with Pseudomonas plecoglossicida and hypoxic stress, indicating that these genes might play pivotal roles in immune function and stress regulation. Protein-protein interaction network analysis further elucidated that PI3K members extensively interacted with key immune signaling molecules such as PDPK1, MTOR, and PTEN, and were enriched in various innate immune-related pathways. Notably, Lcpik3r3b was significantly up-regulated following both acute hypoxia exposure and P. plecoglossicida infection, and was predicted to occupy a central hub in the signaling network. Based on these observations, we further conducted functional verification on Lcpik3r3b and discovered that its recombinant protein could significantly inhibit the proliferation of E. coli. These results would provide valuable insights into the roles of the PI3K family in mediating immune and stress responses in large yellow croaker, and laid a foundation for future investigations into their molecular mechanisms as well as potential applications in aquaculture disease management.
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