A novel alternatively spliced interleukin-1 receptor accessory protein mIL-1RAcP687.
The 570-amino acid membrane form of IL-1RAcP (mIL-1RAcP) plays a pivotal role in the IL-1 signal transduction and response. We have identified another membrane form of IL-1RAcP with 687 amino acids (named as mIL-1RAcP687 hereon). Its except the last amino acid N-terminal 448 amino acid portion, containing three extracellular immunoglobulin domains, one transmembrane domain, and Box 1 and Box 2 of Toll/IL1 Receptor (TIR) domain, is identical to that of mIL-1RAcP. In contrast, the C-terminal 239 amino acid portion of mIL-1RAcP687, containing Box 3 of TIR domain, is unique. The mIL-1RAcP687 splice variant is derived from the first 11 exons except 9b, and a newly identified exon 13 of IL-1RAcP gene, while mIL-1RAcP is derived from the first 12 exons except 9b. Furthermore, mIL-1RAcP687 can associate with proteins involved in the upstream IL-1 signaling pathway such as IL-1RI, Tollip, and MyD88. It thus activates downstream signaling events to activate transcription factor NF-kappaB, and induce the expression of IL-1 responsive genes such as TNF-alpha and GM-CSF. These results demonstrate that like mIL-1RAcP, mIL-1RAcP687 functions in the IL-1 signal transduction and response. Identification of mIL-1RAcP687 adds further complexity to the regulation of IL-1 signaling and its subsequent response.
Lu
Hsin-Lin
HL
Institute of Microbiology and Immunology, School of Life Sciences, National Yang-Ming University, Pei-Tou, Taipei 11221, Taiwan, ROC.
Yang
Chih-Yung
CY
Chen
Hui-Chun
HC
Hung
Chia-Sui
CS
Chiang
Yu-Chi
YC
Ting
Ling-Pai
LP
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D002460:Cell Line; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection
D007375:Interleukin-1; D053577:Interleukin-1 Receptor Accessory Protein; D016328:NF-kappa B