Oncostatin M - Receptors

Receptors

Receptors for OSM can be found on a variety of cells from a variety of tissues. In general cells derived from endothelial and tumour origins express high levels of OSM receptors, whereas cells of Haematopoietic origin tend to express lower numbers. Scatchard analysis of radio ligand binding data from 125I-OSM binding to a variety of OSM responsive cell lines produced curvilinear graphs which the authors interpreted as the presence of two receptor species, a high affinity form with an approximate dissociation constant Kd of 1-10 pM, and a low affinity form of 0.4-1 nM. Subsequently it was shown that the presence of gp130 alone was sufficient to reproduce the low affinity form of the receptor, and co-transfection of COS-7 cells with LIFR and gp130 produced a high affinity receptor. However further experiments demonstrated that not all actions of OSM could be replicated by LIF, that is certain cells that are irresponsive to LIF would respond to OSM. This data hinted to the existence of an additional ligand specific receptor chain which led to the cloning of OSMR. These two receptor complexes, namely gp130/LIFR and gp130/OSMR, were termed the type I and type II Oncostatin-M receptors. The ability of OSM to signal via two receptor complexes conveniently offers a molecular explanation to the shared and unique effects of OSM with respect to LIF. Thus common biological activities of LIF and OSM are mediated through the type I receptor and OSM specific activities are mediated through the type II receptor.

The murine homologue of OSM was not discovered until 1996, whereas the murine OSMR homologue was not cloned until 1998. Until recently, it was thought that mOSM only signals through the murine type II receptor, namely through mOSMR/mgp130 complexes, because of a low affinity for the type I receptor counterpart. However, it is now known that, in bone at least, mOSM is able to signal through both mOSMR/mgp130 and mLIFR/mgp130.

1. REDIRECT