OSM is a cytokine originally isolated from medium conditioned by PMAtreated U 937 human histiocytic leukemia cells based on its ability to inhibit growth of A375 melanoma cells. The human OSM cDNA encodes a 252 amino acid preproOSM polypeptide with a 25 residue hydrophobic signal peptide and a hydrophilic Cterminaldomain that are proteolytically processed to generate the 196 residue mature form of OSM. Although both mature and proOSM are equally active in radioreceptor assays, the mature OSM is 5to 60 fold more active in growth inhibition assays. Thus, proteolytic processing of the proOSM peptide may be important in regulating the in vivo activities of OSM.
OSM is a pleiotropic cytokine that initiates its biological activities by binding to specific cell surface receptors. The gp130, a signal transducing component (β subunit) of the IL6, LIF and CNTF receptor complexes, was identified as a lowaffinity OSM receptor that does not transduce OSM signals. The low affinity LIF receptor (LIF R, a gp130related protein) has now been identified to be a component of a highaffinity OSM receptor that will transduce OSM signals. Since OSM is also active on cells that do not express LIF R, a specific OSM receptor that does not involve LIF R must also exist. Besides its growth inhibitory activities on human A375 melanoma and mouse M1 myeloid leukemic cells, as well as on other solid tumor cells, OSM also has growth stimulatory activities on normal fibroblasts, AIDSKaposi
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