Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10771793 | Biochemical and Biophysical Research Communications | 2005 | 9 Pages |
Abstract
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 30Â min and then returned to basal levels by 1Â h. The gene induction was sensitive to both pharmacological and genetic inhibition of MEK. Leupeptin, a serine protease inhibitor, suppressed Pla but 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.
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Authors
Lirlândia P. De Sousa, Bruno S.A.F. Brasil, Breno M. Silva, Marcelo H.A. Freitas, Sarah V. Nogueira, Paulo C.P. Ferreira, Erna G. Kroon, Cláudio A. Bonjardim,