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Identification and functional characterization of a novel interleukin 17 receptor: a possible mitogenic activation through ras/mitogen-activated protein kinase signaling pathway.

Abstract
Interleukin-17 receptor (IL-17R) is increasingly emerged as a distinct receptor family functioning in diverse cellular processes including inflammation and cancer. In this study, we uncovered a novel member of IL-17R from mouse tissue that was named mouse IL-17RE (mIL-17R). Mouse IL-17RE cDNA is composed of at least 14 exons and presents at least 6 spliced isoforms (mIL-17RE1-6) with a molecular weight ranging from 34.2 to 70.1 kD. Mouse IL-17RE is expressed in limited tissues such as lung, kidney, stomach, intestine and testis, etc., and is mainly localized in the cytoplasm and on cell membrane. IL-17RE can also be detected in numerous tumor cell lines. Importantly, a mitogenic effect was detected in BaF3 cells stably transfected with the chimeric receptor fused by the ectodomain of erythropoietin receptor (EPOR) with the transmembrane and endomain of IL-17RE in a serum-dependent but EPO-independent manner. Moreover, ERK1/2 phosphorylation was significantly up-regulated as the dose of mIL-17RE increased. Specific RNAi targeting at mIL-17RE dramatically inhibited the activation of ERK1/2, indicating that mIL-17RE could functionally activate RAS/MAPK signaling pathway. Using dominant negative MEK (Dn-MEK) or RAS (Dn-RAS) as a signaling blocker, we were able to show that mIL-17RE probably activated RAS/MAPK signaling at or upstream of RAS. Overall, our results strongly indicate that mIL-17RE may belong to a novel growth-receptor like molecule that has the capability to support cellular mitogenesis through RAS/MAPK pathway.
AuthorsTie-Shi Li, Xue-Ni Li, Zhi-Jie Chang, Xin-Yuan Fu, Li Liu
JournalCellular signalling (Cell Signal) Vol. 18 Issue 8 Pg. 1287-98 (Aug 2006) ISSN: 0898-6568 [Print] England
PMID16310341 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Il17ra protein, mouse
  • Ligands
  • Mitogens
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-17
  • Extracellular Signal-Regulated MAP Kinases
  • ras Proteins
Topics
  • Alternative Splicing (genetics)
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Chlorocebus aethiops
  • Computational Biology
  • Dose-Response Relationship, Drug
  • Exons (genetics)
  • Extracellular Signal-Regulated MAP Kinases (metabolism)
  • Gene Expression Profiling
  • Genome (genetics)
  • Humans
  • Introns (genetics)
  • Ligands
  • MAP Kinase Signaling System
  • Mice
  • Mitogens
  • Molecular Sequence Data
  • Phylogeny
  • RNA, Messenger (genetics, metabolism)
  • Receptors, Interleukin (chemistry, genetics, metabolism)
  • Receptors, Interleukin-17
  • Tumor Cells, Cultured
  • ras Proteins (metabolism)

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