P48-Triggered transmembrane signaling transduction of human monocytes:mobilization of calcium ion and activation of protein kinase C(PKC)

作     者：CHANG ZL RE HALL.(Shanghai Institute of Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.)(Dept. of Medicine, Director of Div. of Hematology /On-cology, Univ. of Tennessee Medical Center, Knoxville, TN 37920.) 

作者机构：Shanghai Institute of Cell Biology Chinese Academy of Sciences Shanghai China Dept. of Medicine Director of Div. of Hematology /Oncology Univ. of Tennessee Medical Center Knoxville 

出 版 物：《Cell Research》 (细胞研究(英文版))

年 卷 期：1995年第5卷第1期

页      面：101-114页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

主　　题：P48 monocyte differentiation inducing factor Signal transduction Ca~+ mobilization PKC activation TNF secretion 

摘      要：P48 is a cytokine which induces monocyte differentia-tion and the induction of cytotoxic activity. In this study,the signal transduction events involved in the stimulation of monocytes with the membrane form of P48 (mP48) were investigated. Monocyte stimulation with mP48 was found to involve the mobilization of intracellular calcium (Ca2+)and the activation and translocation of PKC from the cy-tosol to the membrane. Membane P48 induced a rapid rise of intracellular Ca2+ in a dose dependent maner. Simi-larly the stimulation of monocytes with P48 was found to involve the activation and translocation of PKC. The translocation of PKC was rapid (within 0-5 min) yet tran-sient with PKC activity returning to control levels by 8 min. The functional role of protein kineses in P48 induced TNF secretion was studied using various kinese inhibitors. The PKC inhibitors, H-7 and sphingosine, were found to inhibit P48 induced TNF secretion with 50% inhibition at 5μM HA1004, which inhibts cyclic nucleotide-dependent kinase (PKA, Ki 1.2μM), did not inhibit TNF secretion. H-8 (PKA inhibitor) was found to be an effective inhibitor of TNF secretion only at high concentrations(30μp. The Calmodulin-dependent kinase inhibitor, W7 (Ki 12μM)was found to be effective at concentration above 5μ*** findings suggest that P48-triggered TNF secretion involves transmembrane Ca2+ signaling and the subse-quent activation of at least two protein kineses, PKC and CaMK.