Abstract
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 Galpha 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 Galpha i/o, PLC and IP3-dependent pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Calcium / metabolism
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Calcium Signaling / drug effects
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Cell Degranulation / drug effects*
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Cell Degranulation / immunology
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Cell Line
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Enzyme Inhibitors / pharmacology*
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GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
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Humans
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Inositol 1,4,5-Trisphosphate Receptors / metabolism
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Ligands
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Mast Cells / drug effects*
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Mast Cells / enzymology
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Mast Cells / immunology
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Mast Cells / physiology
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Microscopy, Confocal
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Oligopeptides / pharmacology*
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Peptide Library
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / physiology*
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Receptors, G-Protein-Coupled / metabolism
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Substrate Specificity
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Type C Phospholipases / metabolism
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beta-N-Acetylhexosaminidases / metabolism
Substances
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Enzyme Inhibitors
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Inositol 1,4,5-Trisphosphate Receptors
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Ligands
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Oligopeptides
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Peptide Library
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Receptors, G-Protein-Coupled
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myristoyl-SIYRRGARRWRKL
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protein kinase C zeta
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Protein Kinase C
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Type C Phospholipases
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beta-N-Acetylhexosaminidases
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GTP-Binding Protein alpha Subunits, Gi-Go
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Calcium