Binding of PLCδ1PH-GFP to Ptdlns(4,5)P2 prevents inhibition of phospholipase C-mediated hydrolysis of Ptdlns(4,5)P2 by neomycin
Binding of PLCδ1PH-GFP to Ptdlns(4,5)P2 prevents inhibition of phospholipase C-mediated hydrolysis of Ptdlns(4,5)P2 by neomycin作者机构:Department of Pharmacology Hebei Medical University Shijiazhuang China
出 版 物:《Acta Pharmacologica Sinica》 (中国药理学报(英文版))
年 卷 期:2005年第26卷第12期
页 面:1485-1491页
核心收录:
学科分类:1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 1002[医学-临床医学] 100602[医学-中西医结合临床] 10[医学]
基 金:国家自然科学基金 国家科技部项目 国家自然科学基金国家杰出青年科学基金
主 题:phosphatidylinositol 4,5-bisphosphate neomycin phospholipase C pleckstrin homology domains competitive binding acetylcholine green fluorescent proteins
摘 要:Aim:To investigate the effects of the pleckstrin homology(PH)domain of phos-pholipase Cδ1(PLCδ1PH)on inhibition of phospholipase C(PLC)-mediated hy-drolysis of phosphatidylinositol 4,5-bisphosphate[PtdIns(4,5)P2]by ***:A fusion construct of green fluorescent protein(GFP)and PLCδ1PH(PLCδ1PH-GFP),which is known to bind PtdIns(4,5)P2specifically,together withlaser-scanning confocal microscopy,was used to trace PtdIns(4,5)***:Stimulation of the type 1 muscarinic receptor and the bradykinin 2 recep-tor induced a reversible PLCδ1PH-GFP translocation from the membrane to thecytosol in COS-7 *** inhibitor U73122 blocked the ***,a known PtdIns kinase inhibitor,did not affect the translocationinduced by ACh,but blocked recovery after translocation,indicating thatPtdIns(4,5)P2hydrolysis occurs through receptor-mediated PLC ***,a commonly used phospholipase C blocker,failed to block the recep-tor-induced PLCδ1PH-GFP translocation,indicating that neomycin is unable toblock PLC-mediated Ptdlns(4,5)Pe ***,in the absence of PLCδ1PH-GFP expression,neomycin abolished the receptor-induced hydrolysis ofPtdIns(4,5)P2 by ***:Although PLCδ1PH and neomycin bind toPtdIns(4,5)P2 in a similar way,they have distinct effects on receptor-mediatedactivation of PLC and PtdIns(4,5)P2 hydrolysis.