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Leukemia Inhibitory Factor (LIF) acts as an inducer or inhibitor of differentiation and promotes either survival, proliferation, or activation of a wide array of target cells, including hemopoietic, hepatic, adipogenic, osteogenic, renal, neuronal, and embryonic cells (1, 2). LIF action appears to be mediated through specific cellular receptors of high affinity (dissociation constant, K sub d = 1 X 10 sup -11 to 20 X 10 sup -11 M) and low affinity (K sub d = 1 X 10 sup -9 to 3 X 10 sup -9 M) (3). LIF receptor cDNA confers specific low-affinity binding of LIF when expressed in COS-7 cells (1) and both low-affinity and high-affinity binding when expressed in murine B9 cells (4). The LIF receptor is a member of the hematopoietin receptor superfamily (5) and resembles most closely the beta subunit (gp130) of the IL-6 receptor (6, 7) and the granulocyte-colony-stimulating factor (G-CSF) receptor (8). LIF and a second cytokine, Oncostatin M (OSM), are related in structure, chromosomal localization, and biological activity (9). Analysis of the binding of human OSM (hOSM) to native and recombinant LIF receptors on a variety of cell types (4) led to the following conclusions: (i) the high-affinity, but not the low-affinity, LIF receptor is also an OSM receptor; (ii) distinct OSM-specific receptors exist on A375 melanoma cells and H2981 lung carcinoma cells; and (iii) OSM may have all of the biological activities of LIF and also a variety of activities mediated by the OSM-specific receptor.
We expected that a second subunit of the LIF receptor might confer high-affinity binding of LIF and OSM to the cloned LIF receptor. Because hOSM does not bind to the low-affinity hLIF receptor, we used hOSM to screen for this subunit. We expressed the cloned low-affinity hLIF receptor and pools of cDNA clones from a human placental cDNA library in COS-7 cells and screened for binding of sup 125 I-labeled hOSM (10). A pool of cDNAs was identified that conferred hOSM binding in the presence of the hLIF receptor, and a single cDNA clone (B10G) with the same properties was isolated. The cDNA insert of this clone was nearly identical to that of gp130, the high-affinity converter and signal transducing component (beta subunit) of the human IL-6 receptor complex, which...