EFECTS OF ALPHA2-MACROGLOBULIN (ALPHA2-M) ON THE ACTIVATION OF INTRACELLULAR SIGNALING PATHWAYS USING CELLS LINES DIFFERENTIAL EXPRESSION OF alpha 2-M RECEPTOR

CÁCERES LC; BARCELONA PF; CESCHIN DG; BONACCI GA; CHIABRANDO GA.

Pinamar, Buenos Aires Republica Argentina.

Congreso; SAIB 2005 (XLI Reunion Anual de Sociedad Argentina en Bioquimica y Biologia Molecular).; 2005

Sociedad Argentina en Bioquimica y Biologia Molecular

a₂-M is a broad specific plasma proteinase inhibitor. Upon binding to proteinases, it undergoes a major conformational change that exposes receptor recognition, which is named as (a₂M*). Two surface cell receptors have been proposed for a₂M*: LRP-1 and Grp78. Our results and other authors have demonstrated that a₂M* generate cellular proliferation and activate intracellular signaling pathways such as MAPK and PKB. However, the molecular mechanisms about the a₂M* receptors involved are unclear. In this work we investigated the surface cell receptor responsible to mediate the intracellular signaling pathways by a₂M* using cell lines that express constitutively and differentially both a₂M* receptors. With this propose, we used macrophage derived cell line, J774, which is LRP-1(+) and Grp78(-), and the cell line Cho-K1 which is LRP-1(-) and grp78(+). On these cell lines we analyzed the down-stream effect of a₂M*, measuring ERK-MAPK and JNK-MAPK pathways by Western blotting. The main results obtained showed that a₂M* at different concentrations (7, 20, 60 and 180 nM) promoted in J774 and Cho-K1 a differential kinetics of ERK1/2  phosphorilation and C-jun activation.  In conclusion, we demonstrated that a₂M* activates intracellular signaling pathways, which are mediated by LRP-1. In addition, this work constitutes the first evidence that LRP-1 can activate the JNK/MAPK pathways.