A myristoylated pseudosubstrate peptide of PKC-ζ induces degranulation in HMC-1 cells independently of PKC-ζ activity

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-zeta (zeta-PS; myristoyl-SIYRRGARRWRKL, a PKC-zeta inhibitor) regulates mast cell degranulation. zeta-PS increased [Ca+2](i) level at nanomolar concentrations in a PKC-zeta activity-independent manner in HMC-1 cells. Moreover, zeta-PS-induced [Ca+2](i) generation was completely abrogated by phospholipase C (PLC), IP3 receptor or G alpha(i/o). inhibitor and zeta-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 zeta-PS can induce degranulation in HMC-1 cells by triggering the calcium signal via a PKC-zeta-independent but G alpha(i/o), PLC and IP3-dependent pathways. (c) 2008 Elsevier Inc. All rights reserved.