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

doi:10.1016/j.febslet.2011.04.031

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

FEBS Lett. 2011 Jun 23;585(12):1835-40. doi: 10.1016/j.febslet.2011.04.031. Epub 2011 Apr 20.

Authors

Tatsuya Akagi¹, Kouhei Shimizu, Shoukichi Takahama, Takahiro Iwasaki, Kazuhiro Sakamaki, Yaeta Endo, Tatsuya Sawasaki

Affiliation

¹ Cell-Free Science and Technology Research Center, Ehime University, Matsuyama, Ehime, Japan.

PMID: 21524651
DOI: 10.1016/j.febslet.2011.04.031

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis*
Carrier Proteins / metabolism
Caspase 8 / metabolism*
Feedback, Physiological*
HeLa Cells
Humans
Interleukins / metabolism*
Membrane Proteins / metabolism
Peptide Library
Receptors, Interleukin-21 / metabolism*
STAT3 Transcription Factor
Signal Transduction*

Substances

Carrier Proteins
Interleukins
Membrane Proteins
Peptide Library
Receptors, Interleukin-21
STAT3 Transcription Factor
VEZT protein, human
CASP8 protein, human
Caspase 8
interleukin-21