Activated alfa 2-macroglobulin (a2M) mediates intracellular signaling pathways via the endocytic receptor LRP-1.

CÁCERES LEANDRO; BONACCI GUSTAVO; CESCHIN DANILO; CHIABRANDO GUSTAVO

Iguazu

Congreso; XL Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB). (2004).; 2004

Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB)

ACTIVATED ALFA-2 MACROGLOBULIN (a2M*) MEDIATES INTRACELLULAR SIGNALING PATHWAYS VIA THE ENDOCYTIC RECEPTOR LRP-1. Cáceres L., Bonacci G., Ceschin D, Chiabrando G. Depto. Bioquímica Clínica-CIBICI, Fac. Cs. Quím., U.N.C. leandrocaceres@mail.fcq.unc.edu.ar Alfa-2-macroglobulin (a2M) is the most important human proteinase inhibitor, upon binding to proteinases undergoes a conformational change, activated a2M (a2M*), that expose recognition receptor site allowed its interaction with LRP-1 receptor. LRP-1 is a member of the LDL receptor gene family that binds to a variety of ligands, some of which trigger signalling transduction. Previously we have demonstrated that a2M* has proliferative effects and increase intracellular calcium in J774 macrophage derived cell line LRP positive. In this work we evaluate the a2M* effect down-stream to LRP-1 interaction measuring MAPK phosphorylation in J774 cell cultured in the presence and absence of LPS (a down regulator factor of LRP-1). By Western blotting we observe that 2M* 20 nM and 70 nM promote ERK-1/2 phosphorylation at different times (15, 30, and 60 min.). On the other hand, when J774 were treated with LPS 30 ug/ml for 24 hs we demonstrate that intracellular signalling pathways were not activated in the presence of a2M*. In addition, we analyse the a2M* effect on ERK-1/2 phosphorylation in HT-1080 fibroblast derived cell LRP-1 positive. Like J774, a2M* 20 nM and 70 nM promotes ERK-1/2 phosphorylation. In conclusion, in this work we demonstrate that a2M* can activate intracellular signalling pathways mediated by LRP-1.