摘要:SummaryThe mitogen-activated protein kinase (MAPK) intracellular signaling pathway mediates numerous biological processes, including antimicrobial immune response by inducing antimicrobial peptides (AMPs) production. Although MAPK signaling cascade proteins have been identified in penaeid shrimp, their modulation via the MKK4-p38-c-Jun cascade and effect on AMPs production is unknown. Here, we show that hemocyanin (PvHMC), antimicrobial peptides (anti-lipopolysaccharide factor, crustin, and penaeidins), and MKK4-p38-c-Jun cascade proteins are simultaneously induced by pathogens (Vibrio parahaemolyticus,Staphylococcus aureus, and white spot syndrome virus) inPenaeus vannamei. Intriguingly, knockdown ofPvHMCwith or without pathogen challenge attenuated the expression of MKK4-p38-c-Jun cascade proteins and their phosphorylation level, which consequently decreased AMPs expression. Further analysis revealed that PvHMC interacts via its armadillo (ARM) repeat domain with PvMKK4 to modulate the p38 MAPK signaling pathway. Thus, the ARM repeat domain enables penaeid shrimp hemocyanin to modulate AMPs expression during antimicrobial response by activating the p38 MAPK signaling pathway.Graphical abstractDisplay OmittedHighlights•Pathogens induce hemocyanin, MKK4-p38-c-Jun proteins, and antimicrobial peptide genes•Hemocyanin modulates MKK4-p38-c-Jun cascade proteins to regulate AMPs gene expression•Hemocyanin interacts with MKK4 to modulate p38 MAPK signaling in penaeid shrimp•Deletion of the ARM repeat domain attenuates the interaction of hemocyanin with MKK4Cell biology; Immunology