Effects of alpha-2-macroglobulin (a2-M) on the activation of intracellular signalling pathways using cell lines with differential expression of a2-M receptors.

CÁCERES LEANDRO; BARCELONA PABLO; CESCHIN DANILO; BONACCI GUSTAVO; CHIABRANDO GUSTAVO

Pinamar

Congreso; XLI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB) 2005. X Congreso de la Panamerican Association for Biochemistry and Molecular Biology (PABMB) 2005. XX Reunión Anual de la Sociedad Argentina de Neuroquí; 2005

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

EFFECTS OF alpha2-MACROGLOBULIN (a2M) ON THE ACTIVATION OF INTRACELLULAR SIGNALING PATHWAYS USING CELL LINES WITH DIFFERENTIAL EXPRESSION OF a2M RECEPTORS. Cáceres L; Barcelona P; Bonacci, GR; Chiabrando GA. Depto. Bioq. Clínica-CIBICI (CONICET), Fac. Cs. Quím. UNC de Córdoba. E-Mail: leandrocaceres@mail.fcq.unc.edu.ar α2-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 (α2M*). Two surface cell receptors have been proposed for α2M*: LRP-1 and Grp78. Our results and other authors have demonstrated that α2M* generate cellular proliferation and activate intracellular signaling pathways such as MAPK and PKB. However, the molecular mechanisms about the α2M* receptors involved are unclear. In this work we investigated the surface cell receptor responsible to mediate the intracellular signaling pathways by α2M* using cell lines that express constitutively and differentially both α2M* 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 α2M*, measuring ERK-MAPK and JNK-MAPK pathways by Western blotting. The main results obtained showed that α2M* 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 α2M* 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.