| First Author | Graf D | Year | 2008 |
| Journal | Arch Biochem Biophys | Volume | 477 |
| Issue | 2 | Pages | 330-8 |
| PubMed ID | 18593565 | Mgi Jnum | J:141894 |
| Mgi Id | MGI:3820000 | Doi | 10.1016/j.abb.2008.06.009 |
| Citation | Graf D, et al. (2008) Caspase-mediated cleavage of the signal-transducing IL-6 receptor subunit gp130. Arch Biochem Biophys 477(2):330-8 |
| abstractText | The present study characterizes the molecular mechanisms of CD95L-induced inhibition of IL-6 signaling, which is known to mediate hepatoprotective effects in response to various toxins. CD95L-induced caspase activation leads to degradation of gp130, thereby suppressing IL-6-induced phosphorylation of STAT3 (Tyr(705)) and of tyrosine phosphatase SHP2 (Tyr(580)). Degradation of gp130 protein in response to CD95L was largely prevented after inhibition of caspase 3 or 8. Introduction of a point mutation into a newly identified caspase cleavage site located within position 800-806 (DHVDGGD) of the cytoplasmic tail of gp130 leads to cleavage resistance of the respective receptor in an in vitro assay with recombinant active caspase 3. Correspondingly, the release of a C-terminal gp130-cleavage product of approximately 18kDa was also inhibited after mutagenesis of this cleavage motif. In conclusion, this study demonstrates that caspase activation by CD95L antagonizes IL-6 signaling by a caspase-mediated cleavage of gp130 thereby probably counteracting hepatoprotective effects of IL-6. |
