SIGNALING OF TYPE-II ONCOSTATIN-M RECEPTOR

Oncostatin M (OSM), mediates its bioactivities through two different h eterodimer receptors. They both involve the gp130-transducing receptor , which dimerizes with either leukemia inhibitor receptor beta or with OSM receptor beta (OSMR beta) to generate, respectively, type I and t ype II OSM receptors. Co-precipitation of gp130-associated proteins, f low cytometry, polymerase chain reaction, and tyrosine phosphorylation analyses allowed tile characterization of both types of OSM receptors expressed on the surface of different cell lines, It also allowed the detection of a large size protein, p250, that specifically associates to the type II OSM receptor components anti that is tyrosine-phosphor ylated after the activation peak of the gp130.OSMR beta heterocomplex, The restricted expression of type I OSM receptor by the SAR choriocar cinoma cell line, and type II receptor by the A375 melanoma cell line, permitted the characterization of their signaling machineries. Both t ype I and type II OSM receptors activated Jak1, Jak2, and Tyk2 recepto r-associated tyrosine kinases, The information is nest relayed to the nucleus by the STAT3 transcriptional activator, which is recruited by both types of OSM receptors, In addition, STAT5b was specifically acti vated through the gp120.OSMR beta type II heterocomplex. The signaling pathway differences observed between the common type I LIF/OSM recept or and the specific type II OSM receptor might explain some of the bio activities specifically displayed by OSM.