Plasminogen/plasmin regulates c-fos and egr-1 expression via the MEWERK pathway
Plasminogen/plasmin regulates c-fos and egr-1 expression via the MEWERK pathway
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DOI：
10.1016/j.bbrc.2005.01.123
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发表时间：
2005-04-01
影响因子：
3.1
通讯作者：
Bonjardim, CA
中科院分区：
文献类型：
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作者：
De Sousa, LP;Brasil, BSAF;Bonjardim, CA
在本研究中，我们发现纤溶酶原（Plg）和纤溶酶原（Pla）结合到细胞表面的lysine结合位点，并触发激活丝裂原活化蛋白激酶（MAPK） MEK和ERK1/2的信号通路，进而导致主要应答基因c-fos和早期生长应答基因egr-1的表达。我们的数据显示，Plg/ pla刺激的两种基因的稳态mRNA水平在30分钟内达到最大值，然后在1小时内恢复到基础水平。基因诱导对MEK的药理学和遗传抑制都很敏感。丝氨酸蛋白酶抑制剂leeptin抑制Pla bill而非plg诱导的c-fos和egr-1表达，强调了与Pla相关的丝氨酸蛋白酶活性的作用。霍乱毒素的预先孵育完全阻断了Plg/ pla诱导的基因表达，这表明另一种募集G蛋白偶联受体的信号通路也可能参与其中。此外，Plg/Pla还能刺激AP-1和EGR-1的dna结合活性。这些都被MEK的药理抑制所消除。总之，这些结果表明Plg/Pla通过激活MEK/ERK途径刺激c-fos和egr-1的表达。(C) 2005爱思唯尔公司版权所有。
in this study, we showed that plasminogen (Plg) and plasmin (Pla) bind to lysine-binding sites on cell surface and trigger a signaling pathway that activates the mitogen-activated protein kinase (MAPK) MEK and ERK1/2, which in turn leads to the expression of the primary response genes c-fos and early growth response gene egr-1. Our data show that the Plg/Pla-stimulated steady-state mRNA levels of both genes reached a maximum by 30 min and then returned to basal levels by 1 h. The gene induction was sensitive to both pharmacological and genetic inhibition of MEK. Leupeptin, a serine protease inhibitor, suppressed Pla bill not Plg-induced c-fos and egr-1 expression, emphasizing the role played by the serine protease activity associated with Pla. Pre-incubation with cholera toxin completely blocked the Plg/Pla-induced gene expression, suggesting that another signaling pathway, which recruits G protein-coupled receptors, may also be involved. Furthermore, Plg/Pla also stimulated AP-1 and EGR-1 DNA-binding activities. which were abrogated by pharmacological inhibition of MEK. Altogether, these results suggest that Plg/Pla stimulates c-fos and egr-1 expression via activation of the MEK/ERK pathway. (C) 2005 Elsevier Inc. All rights reserved.