Interactions between oncostatin M and the IL-6 signal transducer, gp130

Abstract Recently, gp130, the signal transducer for interleukin 6 (IL-6), leukemia inhibitory factor (LIF), and ciliary neurotrophice factor (CNTF), was identified as the low-affinity receptor for oncostatin M (OM). However, it is not yet clear if OM binding to gp130 requires accessory factor(s) and if gp130 alone can mediate OM signalling. Here we report that: (a) expressing murine gp130 in BAF-B03 cells (BAF-m130) resulted in the appearance of a single class of low-affinity OM binding sites; (b) chemical cross-linking studies with 125 I-OM identified a 180 kDa labelled complex on BAF-m130 cells; (c) OM cross-linking to the H2981 cell line which expresses both low- and high-affinity OM receptor, identified a 180 kDa and an additional 280 kDa species; (d) 125 I-OM was specifically cross-linked to soluble recombinant gp130 (sgp 130-Rg) in solution; and (e) the cellular proliferation of BAF-m130 was unaffected by OM treatment. These data indicate that gp130 can act as the low-affinity receptor for OM, however, gp130-OM interactions alone are unable to elicit cellular proliferation. This suggests that an additional factor(s) are required to interact with the OM/gp130 complex to form the high-affinity functional receptor. We propose that the 280 kDa species detected on H2981 cells is likely a complex of OM, gp130, and the putative β chain of the functional OM high-affinity receptor. Recently, OM has been shown to be the major growth factor for Kaposi's sarcoma derived cells. Since sgp130-Rg can inhibit OM binding to its receptor, it may be useful as a growth inhibitor of Kaposi's sarcoma cells in vitro and in vivo.