title: Caspase-8 cleavage of the interleukin-21 (IL-21) receptor is a negative feedback regulator of IL-21 signaling.
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.
authors.affiliation: Cell-Free Science and Technology Research Center, Ehime University, Matsuyama, Ehime, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Akagi
authors.forename: Kouhei
authors.initials: K
authors.lastname: Shimizu
authors.forename: Shoukichi
authors.initials: S
authors.lastname: Takahama
authors.forename: Takahiro
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sakamaki
authors.forename: Yaeta
authors.initials: Y
authors.lastname: Endo
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawasaki
mesh_terms: D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism*; D025461:Feedback, Physiological; D006367:HeLa Cells; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D019151:Peptide Library; D053655:Receptors, Interleukin-21 / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D000098546:Interleukin-21
chemical_list: D002352:Carrier Proteins; D007378:Interleukins; D008565:Membrane Proteins; D019151:Peptide Library; D053655:Receptors, Interleukin-21; D050796:STAT3 Transcription Factor; C494547:VEZT protein, human; C505530:CASP8 protein, human; D053181:Caspase 8; D000098546:Interleukin-21