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. 2005 Dec 2;337(4):1065-71.
doi: 10.1016/j.bbrc.2005.09.154. Epub 2005 Oct 4.

Plasminogen/plasmin regulates alpha-enolase expression through the MEK/ERK pathway

Lirlândia P Sousa  1 , Breno M Silva, Bruno S A F Brasil, Sarah V Nogueira, Paulo C P Ferreira, Erna G Kroon, Kanefusa Kato, Cláudio A Bonjardim
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Plasminogen/plasmin regulates alpha-enolase expression through the MEK/ERK pathway

Lirlândia P Sousa et al. Biochem Biophys Res Commun. .

Abstract

Previously we have demonstrated that both plasminogen (Plg) and plasmin (Pla) regulate the expression of the transcription factors c-FOS and EGR-1 [L.P. De Sousa, B.S. Brasil, B.M. Silva, M.H. Freitas, S.V. Nogueira, P.C. Ferreira, E.G. Kroon, C.A. Bonjardim, Plasminogen/plasmin regulates c-fos and egr-1 expression via the MEK/ERK pathway, Biochem. Biophys. Res. Commun. 329 (2005) 237-245]. Here we show that Plg activates the mitogen-activated protein kinases MEK and ERK which leads to alpha-enolase (alpha-ENO) gene expression not only in fibroblasts, but also in peripheral blood mononuclear cells. The alpha-ENO mRNA accumulation was apparent three hours post-Plg treatment and remained elevated out to 28h, a process that seems to require both de novo protein synthesis and active gene transcription. Pla mimics Plg-stimulated alpha-ENO expression through its serine protease activity, suggesting that conversion of Plg to active Pla is required. Pharmacological and genetic blockade of MEK caused inhibition of alpha-ENO mRNA accumulation, implicating MEK/ERK as the transduction pathway that leads to alpha-ENO expression upon Plg stimulation. Furthermore, Plg stimulated DNA binding activity of the transcription factors activator-protein 1 and early growth response gene-1 to their cognate regulatory sequences at alpha-ENO promoter. Altogether, our data show that Plg/Pla regulates alpha-ENO expression through the MEK/ERK pathway.

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