TI  - Involvement of <prot>IL-6</prot> signal transducer <prot>gp130</prot> in <prot>IL-11</prot>-mediated signal
      transduction.
PG  - 2555-61
AB  - <prot>IL-11</prot> is a novel cytokine with a variety of biofunctions which overlap
      with those of <prot>IL-6</prot>. We have previously identified <prot>IL-11</prot> specific binding
      protein which is distinct from that of <prot>IL-6</prot> in a number of cell lines. The
      similarities in biofunctions and differences in ligand binding proteins
      between <prot>IL-11</prot> and <prot>IL-6</prot> prompted us to investigate whether <prot>IL-11</prot> shares
      common signal transduction mechanisms with <prot>IL-6</prot>. We have examined early
      signals triggered by <prot>IL-11</prot> or <prot>IL-6</prot> in a multifactor-dependent human
      erythroleukemic cell line, TF-1. The results showed that  <prot>IL-11</prot>  and  <prot>IL-6</prot> 
      can both stimulate cell proliferation, induce similar pattern of protein
      tyrosine phosphorylation, and activate the same proto-oncogene (  <prot>junB</prot>  )
      expression in TF-1 cells. These findings imply that  <prot>IL-11</prot>  and  <prot>IL-6</prot>  share
      similar early signaling events with the possibility of using the same
      signal transducer,   <prot>gp130</prot>  . We next tested whether <prot>IL-11</prot> induced signaling
      can be inhibited by anti-<prot>gp130</prot> antibodies which blocked <prot>IL-6</prot>-mediated
      functions. It was observed that anti-<prot>gp130</prot> antibodies abolished cell
      proliferation, protein tyrosine phosphorylation, and <prot>junB</prot> gene expression
      elicited by <prot>IL-11</prot> or <prot>IL-6</prot> 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-<prot>IL-6R</prot>
      antibody inhibited the ability of <prot>IL-6</prot>, but not <prot>IL-11</prot>, to transduce early
      signals in TF-1 cells. These results demonstrate that <prot>IL-11</prot> and <prot>IL-6</prot>
      utilize different ligand binding proteins, but share common signal
      transducer, <prot>gp130</prot>, in TF-1 cells.
AD  - Department of Medicine (Hematology/Oncology), Indiana University School of
