Dephosphorylation at Ser548 regulates hemocyanin-derived antibacterial peptides and immune defense in Penaeus vannamei.

Phosphorylation plays a critical role in regulating immune responses in invertebrates. In Penaeus vannamei, hemocyanin, a multifunctional immune protein, is cleaved to produce antimicrobial peptides (AMPs) essential for pathogen defense. This study identifies Ser548 phosphorylation of the hemocyanin small subunit (PvHMCs) as a key regulator of trypsin-mediated hemocyanin degradation and antimicrobial peptides production. Dephosphorylation of Ser548, controlled by PvCK2α kinase and PvPP2AC phosphatase, enhances cleavage, generating peptides with strong antibacterial activity against Vibrio parahaemolyticus and Streptococcus iniae. Phosphorylation inhibits this process, reducing peptide production and immune efficacy. In vivo, Ser548 dephosphorylation improves bacterial clearance and enhances shrimp survival. These findings reveal a critical molecular mechanism underlying shrimp immunity and suggest targeting hemocyanin phosphorylation to boost disease resistance in aquaculture.