¦Á2M /LRP induces ERK1/2 Phosphorilation by PKC¦Á/¦Â activation in J774 Cells Comunicaci¨®n oral

CÁCERES LC; S¨¢NCHEZ MC; CHIABRANDO GA

Villa Carlos Paz, C¨®rdoba, Argentina

Congreso; XLIV Reuni¨®n Anual de la Sociedad Argentina de Investigaci¨®n en Bioqu¨ªmica y Biolog¨ªa Molecular (SAIB); 2008

Sociedad Argentina de Investigaci¨®n en Bioqu¨ªmica y Biolog¨ªa Molecular (SAIB)

ST-C07.a2M/LRP-1 INDUCES ERK1/2 PHOSPHORYLATION BYPKC-abI ACTIVATION IN J774 CELLSC¨¢ceres LC, S¨¢nchez MC, Chiabrando GA.CIBICI (CONICET). Dpto. Bioq. Cl¨ªn. F.C.Q., U.N.C., CiudadU n i v e r s i t a r i a , C ¨® rd o b a , A rg e n t i n a . E - m a i l :leandrocaceres@mail.fcq.unc.edu.arLDL receptor-related protein (LRP1) is a LDL receptor gene familymember synthesized and processed into 515-kDa extracellular achain and 85-kDa trans-membrane and intracellular ß chain. LRP-1a chain contains multiple ligand recognition sites and ß chain harbormotifs for endocytosis and intracellular signaling events. a2-macroglobulin-protease complex (a2M*) is recognized by LRP1.Previously we demonstrated that a2M* induces cell proliferationand intracellular MAPK activation. However, the molecularmechanisms that promote this intracellular signaling activation are,at the present, unknown. Herein, we evaluate the putativeparticipation of PKC enzymes and intracellular calcium rise on thea2M*-induced MAPK activation in two macrophage-derived celllines, J774 and RAW 264.7. By Western blot we observed thatcalphostin-C blocks ERK1/2 phosphorylation in J774 and RAW264.7 cells. To know the type of PKC involved, different inhibitorsof PKC isoenzymes were used, such as RO-32-0432, GÖ-6976 androttlerin. We demonstrated that the a2M*-induced ERK1/2phosphorylation was inhibited by PKCa and PKC aßI inhibitors,respectively. When J774 and RAW 264.7 were incubated withBAPTA-AM, the a2M*-induced ERK1/2 phosphorylation was alsofully blocked. Our data demonstrate that a2M*-induced MAPKphosphorylation is mediated by PKCa/aßI activation andintracellular calcium mobilization.