A myristoylated pseudosubstrate peptide of PKC-ζ induces degranulation in HMC-1 cells independently of PKC-ζ activity
A myristoylated pseudosubstrate peptide of PKC-ζ induces degranulation in HMC-1 cells independently of PKC-ζ activity
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DOI：
10.1016/j.lfs.2008.01.005
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发表时间：
2008-03-26
期刊：
影响因子：
6.1
通讯作者：
Suh, Pann-Ghill
中科院分区：
文献类型：
--
作者：
Lim, Seyoung;Choi, Jung Woong;Suh, Pann-Ghill
肥大细胞通过脱颗粒释放多种生物活性物质，在变态反应性疾病和宿主对多种病原体的防御中发挥核心作用。在本研究中，我们发现PKC-Zeta(Zeta-PS；Myristoyl-SIYRRGARRWRKL，一种PKC-Zeta抑制剂)的肉豆蔻酰化假底物调节肥大细胞脱颗粒。Zeta-PS以非活性的PKC-Zeta方式增加HMC-1细胞纳摩尔浓度下的[Ca+2](I)水平。此外，Zeta-PS诱导的[Ca+2](I)生成可被磷脂酶C(PLC)、IP3受体或Gα(i/o)完全阻断。抑制剂和Zeta-PS能有效地诱导HMC-1细胞脱颗粒，而PLC抑制剂或钙络合剂可明显抑制这种脱颗粒。因此，我们的结果表明，Zeta-PS可以通过触发钙信号来诱导HMC-1细胞脱颗粒，该信号途径不依赖于PKC-Zeta，但依赖于Gα(i/o)、PLC和IP3。(C)2008 Elsevier Inc.保留所有权利。
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.