CLONING AND CHARACTERIZATION OF A SPECIFIC RECEPTOR FOR MOUSE ONCOSTATIN-M

Oncostatin M (OSM) is a member of a family of cytokines that includes ciliary neurotrophic factor, interleukin-6, interleukin-11, cardiotrop hin-1, and leukemia inhibitory factor (LIF), The receptors for these c ytokines consist of a common signaling subunit, gp130, to which other subunits are added to modify ligand specificity. We report here the is olation and characterization of a cDNA encoding a subunit of the mouse OSM receptor. In NIH 3T3 cells (which endogenously express gp130, LIF receptor beta [LIFR beta], and the protein product, c12, of the cDNA described here), mouse LIF, human UF, and human OSM signaled through r eceptors containing the LIFR beta and gp130 but not through the mouse OSM receptor. Mouse OSM, however, signaled only through a c12-gp130 co mplex; it did not use the LIF receptor. Binding studies demonstrated t hat mouse OSM associated directly with either the c12 protein or gp130 , These data highlight the species-specific differences in receptor ut ilization and signal transduction between mouse and human OSM, In mous e cells, only mouse OSM is capable of activating the mouse OSM recepto r; human OSM instead activates the LIF receptor. Therefore, these data suggest that all previous studies with human OSM in mouse systems did not elucidate the biology of OSM but, rather, reflected the biologica l actions of LIF.