Interactions between oncostatin M and the IL-6 signal transducer, gp130.
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)
Liu
J
J
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Modrell
B
B
Aruffo
A
A
Scharnowske
S
S
Shoyab
M
M
D000818:Animals; D015703:Antigens, CD; D002460:Cell Line; D002522:Chlorocebus aethiops; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D053683:Oncostatin M; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*; D018121:Receptors, Cytokine / Q000302:isolation & purification / Q000378:metabolism*; D053677:Receptors, Oncostatin M; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000473:pathology; D015398:Signal Transduction; D013936:Thymidine / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D016207:Cytokines; D006131:Growth Inhibitors; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D015850:Interleukin-6; D008562:Membrane Glycoproteins; C508351:OSM protein, human; C508352:Osm protein, mouse; D010455:Peptides; D018121:Receptors, Cytokine; D053677:Receptors, Oncostatin M; D011993:Recombinant Fusion Proteins; D053683:Oncostatin M; D050822:Cytokine Receptor gp130; D004247:DNA; D013936:Thymidine