单（ADP-核糖基）转移酶在介导中性粒细胞趋化性的信号通路中的可能作用。 - Suppr | 超能文献

单（ADP-核糖基）转移酶在介导中性粒细胞趋化性的信号通路中的可能作用。

A possible role for mono (ADP-ribosyl) transferase in the signalling pathway mediating neutrophil chemotaxis.

Allport J R, Donnelly L E, Kefalas P, Lo G, Nunn A, Yadollahi-Farsani M, Rendell N B, Murray S, Taylor G W, MacDermot J

Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, UK.

Br J Clin Pharmacol. 1996 Jul;42(1):99-106. doi: 10.1046/j.1365-2125.1996.37014.x.

Abstract

Mono(ADP-ribosyl)transferase activity has been identified on the external surface of human polymorphonuclear neutrophil leucocytes (PMNs). The enzyme is released from the plasma membrane by phosphoinositide-specific phospholipase C, suggesting a glycosylphosphatidylinositol (GPI) linkage of the enzyme to the plasma membrane. Partial sequence of cDNA encoding the enzyme suggests that it is identical to the GPI-linked mono(ADP-ribosyl)-transferase identified previously on human skeletal muscle. 2. A panel of inhibitors of mono(ADP-ribosyl)transferase (including vitamins K1 and K3, novobiocin and nicotinamide) showed a rank order of inhibitory potency similar to that described for other mono(ADP-ribosyl)transferases. Furthermore, the mono(ADP-ribosyl)ation of agmatine was inhibited also by diethylamino (benzylidineamino)guanidine (DEA-BAG), another substrate of the enzyme related structurally to arginine. 3. There was a close linear correlation between the IC50 values for inhibition of mono(ADP-ribosyl)ation of agmatine by DEA-BAG or the enzyme inhibitors and their IC50 values for inhibition of receptor-dependent polymerization of cytoskeletal actin and chemotaxis. 4. These results suggest a role for mono(ADP-ribosyl)transferase in the transduction pathway involved in receptor-dependent re-alignment of the cytoskeleton during neutrophil chemotaxis.

摘要

已在人多形核中性粒细胞（PMN）的外表面鉴定出单（ADP - 核糖基）转移酶活性。该酶由磷酸肌醇特异性磷脂酶C从质膜释放，提示该酶与质膜通过糖基磷脂酰肌醇（GPI）连接。编码该酶的cDNA部分序列表明，它与先前在人骨骼肌上鉴定出的GPI连接的单（ADP - 核糖基）转移酶相同。2. 一组单（ADP - 核糖基）转移酶抑制剂（包括维生素K1和K3、新生霉素和烟酰胺）显示出的抑制效力顺序与其他单（ADP - 核糖基）转移酶所描述的相似。此外，胍丁胺的单（ADP - 核糖基）化也受到二乙氨基（苄叉氨基）胍（DEA - BAG）的抑制，DEA - BAG是该酶的另一种底物，在结构上与精氨酸相关。3. DEA - BAG或酶抑制剂对胍丁胺单（ADP - 核糖基）化的IC50值与它们对细胞骨架肌动蛋白受体依赖性聚合和趋化性抑制的IC50值之间存在密切的线性相关性。4. 这些结果表明单（ADP - 核糖基）转移酶在中性粒细胞趋化过程中参与受体依赖性细胞骨架重新排列的转导途径中发挥作用。