INVOLVEMENT OF IL-6 SIGNAL TRANSDUCER GP130 IN IL-11-MEDIATED SIGNAL-TRANSDUCTION

IL-11 is a novel cytokine with a variety of biofunctions which overlap with those of IL-6. We have previously identified IL-11 specific bind ing protein which is distinct from that of IL-6 in a number of cell li nes. The similarities in biofunctions and differences in ligand bindin g proteins between IL-11 and IL-6 prompted us to investigate whether I L-11 shares common signal transduction mechanisms with IL-6. We have e xamined early signals triggered by IL-11 or IL-6 in a multifactor-depe ndent human erythroleukemic cell line, TF-1. The results showed that I L-11 and IL-6 can both stimulate cell proliferation, induce similar pa ttern of protein tyrosine phosphorylation, and activate the same proto -oncogene (junB) expression in TF-1 cells. These findings imply that I L-11 and IL-6 share similar early signaling events with the possibilit y of using the same signal transducer, gp130. We next tested whether I L-11 induced signaling can be inhibited by anti-gp130 antibodies which blocked IL-6-mediated functions. It was observed that anti-gp130 anti bodies abolished cell proliferation, protein tyrosine phosphorylation, and junB gene expression elicited by IL-11 or IL-6 in TF-1 cells. The same antibodies, however, had no effect on granulocyte-macrophage col ony stimulating factor or erythropoietin-induced TF-1 cell proliferati on. Finally, anti-IL-6R antibody inhibited the ability of IL-6, but no t IL-11, to transduce early signals in TF-1 cells. These results demon strate that IL-11 and IL-6 utilize different ligand binding proteins, but share common signal transducer, gp130, in TF-1 cells.