A myristoylated pseudosubstrate peptide of PKC-zeta induces degranulation in HMC-1 cells independently of PKC-zeta 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 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.
Lim
Seyoung
S
Department of Life Science, Division of Molecular and Life Science, Biotech Center, Pohang University of Science and Technology, San 31 Hyoja-Dong, Nam-Gu, Pohang, Kyungbuk 790-784, Republic of Korea.
Choi
Jung Woong
JW
Kim
Hyeon Soo
HS
Kim
Yun-Hee
YH
Yea
Kyungmoo
K
Heo
Kyun
K
Kim
Jong Hyun
JH
Kim
Sun-Hee
SH
Song
Minseok
M
Kim
Jae Il
JI
Ryu
Sung Ho
SH
Suh
Pann-Ghill
PG
D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D008024:Ligands; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000502:physiology; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000494:pharmacology*; D019151:Peptide Library; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism; D000099221:Protein Kinase C zeta
D002118:Calcium; D004791:Enzyme Inhibitors; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008024:Ligands; D009842:Oligopeptides; D019151:Peptide Library; D011493:Protein Kinase C; D043562:Receptors, G-Protein-Coupled; D010738:Type C Phospholipases; D001619:beta-N-Acetylhexosaminidases; D000099221:Protein Kinase C zeta; C529317:myristoyl-SIYRRGARRWRKL