Endogenous mono-ADP-ribosylation mediates smooth muscle cell proliferation and migration via protein kinase N-dependent induction of c-fos expression.
Endogenous mono-ADP-ribosylation mediates smooth muscle cell proliferation and migration via protein kinase N-dependent induction of c-fos expression.
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内源性单 ADP 核糖基化通过蛋白激酶 N 依赖性诱导 c-fos 表达来介导平滑肌细胞增殖和迁移。
DOI：
10.1046/j.1432-1033.2003.03366.x
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
P. Zahradka
中科院分区：
文献类型：
--
作者：
L. Yau;Brenda Litchie;Shawn Thomas;Benjamin Storie;N. Yurkova;P. Zahradka
ADP核糖化与细胞内与平滑肌细胞血管反应性、细胞骨架完整性和自由基损伤有关。此外，有证据表明，ADP-核糖化是平滑肌细胞增殖所必需的。我们的研究使用了选择性的抑制剂来证实，刺激有丝分裂原合成DNA所必需的是单-ADP-核糖化而不是多-ADP-核糖化。有丝分裂原处理同时增加了可溶性和颗粒单-ADP-核糖基转移酶的活性，以及修饰蛋白的数量。精氨酸依赖的单-ADP-核糖化的选择性诱饵底物--间碘苯甲基胍(MIBG)的加入阻止了这些蛋白质的修饰。MIBG还阻断DNA和RNA合成的刺激，阻止平滑肌细胞迁移，抑制c-fos和c-myc基因表达的诱导。对相关信号转导通路的研究表明，MIBG不干扰MAP激酶和磷脂酰肌醇3-激酶的刺激，但它确实抑制了Rho效应器PRK1/2的磷酸化。这一新的观察表明，单ADP核糖化参与了Rho依赖的信号通路，这是即刻早期基因表达所必需的。
ADP-ribosylation has been coupled to intracellular events associated with smooth muscle cell vasoreactivity, cytoskeletal integrity and free radical damage. Additionally, there is evidence that ADP-ribosylation is required for smooth muscle cell proliferation. Our investigation employed selective inhibitors to establish that mono-ADP-ribosylation and not poly(ADP-ribosyl)ation was necessary for the stimulation of DNA synthesis by mitogens. Mitogen treatment increased concomitantly the activity of both soluble and particulate mono-ADP-ribosyltransferase, as well as the number of modified proteins. Inclusion of meta-iodobenzylguanidine (MIBG), a selective decoy substrate of arginine-dependent mono-ADP-ribosylation, prevented the modification of these proteins. MIBG also blocked the stimulation of DNA and RNA synthesis, prevented smooth muscle cell migration and suppressed the induction of c-fos and c-myc gene expression. An examination of relevant signal transduction pathways showed that MIBG did not interfere with MAP kinase and phosphatidylinositol 3-kinase stimulation; however, it did inhibit phosphorylation of the Rho effector, PRK1/2. This novel observation suggests that mono-ADP-ribosylation participates in a Rho- dependent signalling pathway that is required for immediate early gene expression.
影响因子：
33.6
作者：
G. Owens
通讯作者：
G. Owens
糖基磷脂酰肌醇锚定、分泌和细胞内脊椎动物单 ADP-核糖基转移酶的表征。
影响因子：
8.9
作者：
Okazaki,IJ;Moss,J
通讯作者：
Moss,J
体外微管蛋白 ADP 核糖基化会导致组装抑制和快速解聚。
影响因子：
2.9
作者：
Scaife,RM;Wilson,L;Purich,DL
通讯作者：
Purich,DL