Plasminogen/plasmin regulates alpha-enolase expression through the MEK/ERK pathway.
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.
Sousa
Lirlândia P
LP
Grupo de Transdução de Sinal, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
Silva
Breno M
BM
Brasil
Bruno S A F
BS
Nogueira
Sarah V
SV
Ferreira
Paulo C P
PC
Kroon
Erna G
EG
Kato
Kanefusa
K
Bonjardim
Cláudio A
CA
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005341:Fibrinolysin / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010958:Plasminogen / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D010958:Plasminogen; D004247:DNA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D005341:Fibrinolysin; D010751:Phosphopyruvate Hydratase