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 binding protein which is distinct from that of IL-6 in a number of cell lines. The similarities in biofunctions and differences in ligand binding proteins between IL-11 and IL-6 prompted us to investigate whether IL-11 shares common signal transduction mechanisms with IL-6. We have examined early signals triggered by IL-11 or IL-6 in a multifactor-dependent human erythroleukemic cell line, TF-1. The results showed that IL-11 and IL-6 can both stimulate cell proliferation, induce similar pattern of protein tyrosine phosphorylation, and activate the same proto-oncogene (junB) expression in TF-1 cells. These findings imply that IL-11 and IL-6 share similar early signaling events with the possibility of using the same signal transducer, gp130. We next tested whether IL-11 induced signaling can be inhibited by anti-gp130 antibodies which blocked IL-6-mediated functions. It was observed that anti-gp130 antibodies 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 colony stimulating factor or erythropoietin-induced TF-1 cell proliferation. Finally, anti-IL-6R antibody inhibited the ability of IL-6, but not IL-11, to transduce early signals in TF-1 cells. These results demonstrate that IL-11 and IL-6 utilize different ligand binding proteins, but share common signal transducer, gp130, in TF-1 cells.
Yin
T
T
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202.
Taga
T
T
Tsang
M L
ML
Yasukawa
K
K
Kishimoto
T
T
Yang
Y C
YC
D000818:Animals; D015703:Antigens, CD; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130; D016758:Genes, jun; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D000090063:Proto-Oncogene Mas; D011971:Receptors, Immunologic / Q000502:physiology*; D019947:Receptors, Interleukin-6; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D017370:Interleukin-11; D015850:Interleukin-6; C000715470:MAS1 protein, human; D008562:Membrane Glycoproteins; D000090063:Proto-Oncogene Mas; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D014443:Tyrosine