LIF and OM directly interact with a soluble form of gp130, the IL-6 receptor signal transducing subunit.
Oncostatin M and LIF are related members of a cytokine family that also includes IL-6, CNTF and G-CSF. These proteins exhibit overlapping biological properties and with the exception of G-CSF, they all appear to utilize gp130 as a signaling component of their high affinity receptor complexes. Recently it has been demonstrated that monomeric, membrane bound gp130 can directly bind OM. To further investigate the binding properties of gp130 we generated a soluble form of gp130, sgp130-Rg, to investigate potential gp130 interactions with OM and other members of this cytokine family. Using chemical crosslinking techniques we demonstrate that OM and LIF but not CNTF or IL-6 directly interact with sgp130-Rg. Since OM signaling can be prevented by binding gp130 with anti gp130 mAbs we also investigated the potential of sgp130-Rg to prevent the biological activities of both LIF and OM. Here we demonstrate that sgp130-Rg can bind LIF and OM preventing their biological activities on the TF-1 erythroleukemia cell line. This property suggests that sgp130-Rg may have therapeutic value in the specific prevention of LIF or OM mediated pathologies.
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
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B
Modrell
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Liu
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Miller
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M
Shoyab
D000818:Animals; D015703:Antigens, CD; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D020934:Ciliary Neurotrophic Factor; D003432:Cross-Linking Reagents; D050822:Cytokine Receptor gp130; D016207:Cytokines; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007377:Interleukin-3 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D007457:Iodine Radioisotopes; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000502:physiology*; D019947:Receptors, Interleukin-6; D015398:Signal Transduction; D014162:Transfection / Q000379:methods
D015703:Antigens, CD; D002352:Carrier Proteins; D020934:Ciliary Neurotrophic Factor; D003432:Cross-Linking Reagents; D016207:Cytokines; D006131:Growth Inhibitors; C494200:Il6st protein, mouse; D007377:Interleukin-3; D015850:Interleukin-6; D007457:Iodine Radioisotopes; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C508352:Osm protein, mouse; D010455:Peptides; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D053683:Oncostatin M; D050822:Cytokine Receptor gp130