Mast cells play a central role in allergic disease and host defense against several pathogens through the release of various bioactive compounds via degranulation. In this study, we found that a myristoylated pseudosubstrate of PKC-ζ (ζ-PS; myristoyl-SIYRRGARRWRKL, a PKC-ζ inhibitor) regulates mast cell degranulation. ζ-PS increased [Ca+2]i level at nanomolar concentrations in a PKC-ζ activity-independent manner in HMC-1 cells. Moreover, ζ-PS-induced [Ca+2]i generation was completely abrogated by phospholipase C (PLC), IP3 receptor or Gαi/o inhibitor and ζ-PS potently induced degranulation in HMC-1 cells which was significantly inhibited by pretreating PLC inhibitors or a calcium chelator. Therefore, our results suggest that ζ-PS can induce degranulation in HMC-1 cells by triggering the calcium signal via a PKC-ζ-independent but Gαi/o, PLC and IP3-dependent pathways.
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