Oncostatin M, also known as OSM, is a protein that is encoded by the OSM gene in humans. It is a pleiotropic cytokine that is a part of the interleukin 6 set of cytokines. Of these cytokines, it is linked most closely to leukaemia inhibitory factor, both in terms of its structure and function. However, as of yet, this protein is still poorly defined but is currently providing important for liver development, hematopoiesis, inflammation, and potentially also the possibility of CNS development. This protein is also associated with the formation and destruction of bones. How OSM signals is through the surface of cell receptors that contain the protein gp130; there are two types of receptors, with type 1 composed of gp130 and type 2 made up of gp130 and OSMR.
Originally, OSM in human form was isolated in 1986 when the growth media of PMA treated U-937 histiocytic lymphoma cells by the ability to prevent the growth of cell lines that come from melanomas and other hard solid tumours. OSM is a strong protein and is stable between pH2 and 11 and is resistant to heating of 56 degrees for up to one hour. It was a partial amino acid sequence that allowed the isolation of human OSM cDNA and any genomic clones.
Made up of 196 residues, OSM is the predominant form which has been isolated from a variety of cell lines and relates well to a glycoprotein of 28 KDa, while the larger 227 residue pro-OSM can be unlinked from transfected cells. Pro-OSM, although less effective in growth assays, does display similar binding ability in regards to cell radio ligand binding assays. This means that post translational processing may play a vital role in the in vivo function that OSM has. Like many cytokines, OSM is created from cells by de novo synthesis, which is followed by the release via the classical secretion route. However, OSM can also be released via preformed stores within polymorphonuclear leukocytes.
The primary sequence analysis of OSM links it to the gp130 group of cytokines. This protein most resembles LIF, bearing a 22% identity to it, as well as a 30% similarity. The genes for OSM and LIF occur in tandem on the human chromosome 22, and both have very similar gene structures, sharing similar promoter features and intron-exon structure.
When it comes to gene duplication, data suggests that both OSM and LIF are relatively recently evolved. Out of the five cysteine residues within the OSM sequence in humans, four take part in disulfide bridges, one of these bonds (usually between helices A and B) is required for OSM activity.
OSM’s three-dimensional structure has been solved to atomic resolution, which predicts the long chain, four-helix bundle. When you compare this structure with the known structures of other LC cytokines, it shows that it is most closely linked to LIF. A distinct kink in its A helix comes from the removal of the classical alpha helical H-bonding pattern, a feature that is shared with all structures of LIF.