Caspase-8 cleavage of the interleukin-21 (IL-21) receptor is a negative feedback regulator of IL-21 signaling

Tatsuya Akagi, Kouhei Shimizu, Shoukichi Takahama, Takahiro Iwasaki, Kazuhiro Sakamaki, Yaeta Endo, Tatsuya Sawasaki

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We screened a library of human single-transmembrane proteins (sTMPs), produced by a cell-free system, using a luminescent assay to identify those that can be cleaved by caspase-8 (CASP8). Of the 407 sTMPs screened, only the interleukin-21 receptor (IL21R), vezatin (VEZT), and carbonic anhydrase XIV were cleaved at Asp344, Asp655 and Asp53, respectively. We confirmed that IL21R and VEZT were also cleaved in apoptotic HeLa cells with the cleavage sites. Interestingly, IL21R was cleaved within 30 min after apoptosis induction. Furthermore the CASP8-cleaved form of IL21R did not induce phosphorylation at Tyr705 of STAT3. Our results suggest that the interleukin-21 signaling cascade is negatively regulated by CASP8.

Original languageEnglish
Pages (from-to)1835-1840
Number of pages6
JournalFEBS Letters
Volume585
Issue number12
DOIs
Publication statusPublished - 2011 Jun 23
Externally publishedYes

Keywords

  • Apoptosis
  • Caspase-8
  • Cell-free system
  • Cytokines
  • Interleukin-21

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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  • Cite this

    Akagi, T., Shimizu, K., Takahama, S., Iwasaki, T., Sakamaki, K., Endo, Y., & Sawasaki, T. (2011). Caspase-8 cleavage of the interleukin-21 (IL-21) receptor is a negative feedback regulator of IL-21 signaling. FEBS Letters, 585(12), 1835-1840. https://doi.org/10.1016/j.febslet.2011.04.031