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Interactions between oncostatin M and the IL-6 signal transducer, gp130
1Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
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 125I-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) 125I-OM was specifically cross-linked to soluble recombinant gp130 (sgp130-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 beta 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Oncostatin M (OM) binds to gp130 as a low-affinity receptor, but requires additional factors for high-affinity signaling and cellular proliferation. This suggests a complex receptor formation for OM
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- gp130 is a signal transducer for IL-6, LIF, and CNTF.
- gp130 was recently identified as a low-affinity receptor for Oncostatin M (OM).
- The precise mechanism of OM binding and signaling via gp130 is not fully understood.
Purpose of the Study:
- To investigate if OM binding to gp130 requires accessory factors.
- To determine if gp130 alone can mediate OM signaling.
- To characterize the OM receptor complex.
Main Methods:
- Expressing murine gp130 in BAF-B03 cells (BAF-m130).
- Chemical cross-linking studies using 125I-OM.
- OM cross-linking experiments on H2981 cells.
- Cross-linking 125I-OM to soluble recombinant gp130 (sgp130-Rg).
Main Results:
- BAF-m130 cells exhibited low-affinity OM binding sites.
- A 180 kDa labeled complex was identified on BAF-m130 cells.
- H2981 cells showed 180 kDa and 280 kDa OM cross-linked species.
- OM treatment did not affect BAF-m130 cell proliferation.
- 125I-OM specifically cross-linked to sgp130-Rg.
Conclusions:
- gp130 functions as the low-affinity OM receptor.
- gp130-OM interaction alone does not induce cellular proliferation.
- Additional factors are necessary to form the high-affinity functional OM receptor.
- The 280 kDa species likely represents the complete high-affinity OM receptor complex.