Oncostatin M(OSM) is a cytokine originally isolated from medium conditioned by PMA-treated U-937 histiocytic leukemia cells based on its ability to inhibit growth of A375 melanoma cells. The OSM cDNA encodes a 252 amino acid pre-pro-OSM polypeptide with a 25 residue hydrophobic signal peptide and a hydrophilic C-terminal domain that are proteolytically processed to generate the 196 residue mature form of OSM. Although both mature and pro-OSM are equally active in radio-receptor assays, the mature OSM is 5- to 60-fold more active in growth inhibition assays. Thus, proteolytic processing of the pro-OSM 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.