Oncostatin M - Discovery, Isolation and Cloning

Discovery, Isolation and Cloning

The human form of OSM was originally isolated in 1986 from the growth media of PMA treated U-937 histiocytic lymphoma cells by its ability to inhibit the growth of cell lines established from melanomas and other solid tumours. A robust protein, OSM is stable between pH2 and 11 and resistant to heating for one hour at 56 °C. A partial amino acid sequence allowed the isolation of human OSM cDNA and subsequently genomic clones. The full cDNA clone of hOSM encodes a 252 amino acid precursor, the first 25 amino acids of which functions as a secretory signal peptide, which on removal yields the soluble 227 amino acid pro-OSM. Cleavage of the C-terminal most 31 residues at a trypsin like cleavage site yields the fully active 196 residue form. Two potential N-glycosylation sites are present in hOSM both of which are retained in the mature form.

The 196 residue OSM is the predominant form isolated form a variety of cell lines and corresponds to a glycoprotein of 28 KDa, although the larger 227 residue pro-OSM can be isolated from over transfected cells. Pro-OSM although an order of magnitude less efficacious in growth inhibition assays, displays similar binding affinity toward cells in radio ligand binding assays. Thus post translational processing may play a significant role in the in vivo function of OSM. Like many cytokines OSM is produced from cells by de novo synthesis followed by release through the classical secretion pathway. However, OSM can be released from preformed stores within polymorphonuclear leukocytes on degranulation. It still remains unclear how OSM is targeted to these intracellular compartments.