DETECTION OF RECEPTORS FOR INTERLEUKIN-6, INTERLEUKIN-11, LEUKEMIA INHIBITORY FACTOR, ONCOSTATIN-M, AND CILIARY NEUROTROPHIC FACTOR IN BONE-MARROW STROMAL OSTEOBLASTIC CELLS

The functional receptor complexes assembled in response to interleukin -6 and -11 (IL-6 and IL-11), leukemia inhibitory factor (LIF), oncosta tin M (OSM), and ciliary neurotrophic factor (CNTF), all involve the s ignal transducer gp130: IL-6 and IL-11 induce homodimerization of gp13 0, while the rest heterodimerize gp130 with other gp130-related beta s ubunits, Some of these cytokines (IL-6, IL-11, and CNTF) also require a specificity-determining alpha subunit not directly involved in signa ling. We have searched for functional receptor complexes for these cyt okines in cells of the bone marrow stromal/osteoblastic lineage, using tyrosine phosphorylation of the beta subunits as a detection assay. C ollectively, murine calvaria cells, bone marrow-derived murine cell li nes (+/+LDA11 and MBA13.2), as well as murine (MC3T3-E1) and human (MG -63) osteoblast-like cell lines displayed all the previously recognize d alpha and beta subunits of this family of receptors. However, indivi dual cell types had different constellations of alpha and beta subunit s, In addition and in difference to the other cell types examined, MC3 T3-E1 cells expressed a heretofore unrecognized form of gp130; and MG- 63 displayed an alternative form (type II) of the OSM receptor. These findings establish that stromal/osteoblastic cells are targets for the actions of all the members of the cytokine subfamily that shares the gp130 signal transducer; and suggest that different receptor repertoir es may be expressed at different stages of differentiation of this lin eage.