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首页> 外文期刊>Journal of Cellular Physiology >FGF2-mediated upregulation of urokinase-type plasminogen activator expression requires a MAP-kinase dependent activation of poly(ADP-ribose) polymerase.
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FGF2-mediated upregulation of urokinase-type plasminogen activator expression requires a MAP-kinase dependent activation of poly(ADP-ribose) polymerase.

机译:FGF2-mediated upregulation urokinase-type的纤溶酶原激活物表达需要map激酶依赖的激活保利(ADP-ribose)聚合酶。

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摘要

Poly(ADP-ribosyl)ation is a post-translational modification of protein occurring in the nucleus by poly(ADP-ribose) polymerase enzyme activity. The main role of poly(ADP-ribose) polymerase system as "nick sensor" and DNA breaks repair is based on its activation via DNA strand breaks. Furthermore, poly(ADP-ribose) polymerase modifies the binding to DNA of several transcriptional factors by poly(ADP-ribosyl)ation, thereby regulating also transcriptional gene expression. We have analyzed whether poly(ADP-ribose) polymerase activity is involved in basic fibroblast growth factor (FGF2)-mediated upregulation of urokinase-type plasminogen activator (uPA) mRNA. We demonstrated that specific inhibition of poly(ADP-ribose) polymerase activity via 3-aminobenzamide (3ABA) or NAD+ deprivation prevents FGF2-mediated uPA mRNA over-expression and cell-associated plasminogen activator (PA) production in GM7373 endothelial cell line. We verified that FGF2 stimulates poly(ADP-ribose) polymerase activity by a DNA strand breaks-independent manner which involves a mitogen-activated protein kinases (MAPK)-dependent pathway, as confirmed by using PD98059 inhibitor and anisomycin stimulation. Poly(ADP-ribose) polymerase involved in this mechanism is mainly the 60 kDa molecular mass isoform, that presents an increase in serine phosphorylation in the presence of FGF2.
机译:保利(ADP-ribosyl)是一种翻译后修饰的蛋白质发生在细胞核保利(ADP-ribose)聚合酶的活动。保利(ADP-ribose)聚合酶的主要作用系统“尼克传感器”和DNA断裂修复基于其激活通过DNA链断裂。此外,聚(ADP-ribose)聚合酶修改绑定几个转录的DNA从而由保利(ADP-ribosyl)因素,调节转录的基因表达。我们分析了保利(ADP-ribose)是否聚合酶是参与基本的活动纤维母细胞生长因子(FGF2)介导的的upregulation urokinase-type plasminogen活化剂(uPA) mRNA。特定的抑制聚(ADP-ribose)聚合酶活性通过3-aminobenzamide (3 aba)或剥夺NAD +防止FGF2-mediated uPA信使rna表达和细胞相关在GM7373纤溶酶原激活物(PA)生产内皮细胞线。刺激保利(ADP-ribose)聚合酶的活动由一个DNA链breaks-independent方式涉及到一个增殖蛋白激酶(MAPK)端依赖途径,证实了通过使用PD98059抑制剂和茴香霉素刺激。保利(ADP-ribose)聚合酶参与机制主要是60 kDa分子质量同种型,呈现出一种丝氨酸的增加磷酸化FGF2的存在。

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