|Detection of IL‑17 RD/SEF in K562 Human Cell Line by Flow Cytometry. K562 human chronic myelogenous leukemia cell line was stained with Goat Anti-Human IL‑17 RD/SEF Antigen Affinity-purified Polyclonal Antibody (Catalog # AF2275, filled histogram) or isotype control antibody (Catalog # AB-108-C, open histogram), followed by Phycoerythrin-conjugated Anti-Goat IgG Secondary Antibody (Catalog # F0107).|
|IL‑17 RD/SEF in Human Kidney. IL‑17 RD/SEF was detected in immersion fixed paraffin-embedded sections of human kidney using 15 µg/mL Goat Anti-Human IL‑17 RD/SEF Antigen Affinity-purified Polyclonal Antibody (Catalog # AF2275) overnight at 4 °C. Tissue was stained with the Anti-Goat HRP-DAB Cell & Tissue Staining Kit (brown; Catalog # CTS008) and counterstained with hematoxylin (blue). Specific labeling was localized to the cytoplasm of glomerulli and endothelial cells in capillaries in connective tissue. View our protocol for Chromogenic IHC Staining of Paraffin-embedded Tissue Sections.|
Interleukin-17 receptor D (IL-17 RD), also known as SEF (similar expression to FGFs), is a type I transmembrane protein that is found in both the cytoplasm and plasma membrane (1-5). The gene for this protein belongs to a synexpression group originally identified in zebrafish where SEF is expressed along with FGF-3, -8, sprouty-2 (SPRY2) and SPRY4 (6, 7). By alternate splicing, two transcript variants, potentially encoding three protein isoforms, exist. One is a full-length long form, one a shortened form that uses an alternate start site, and one an alternate splice form that removes the classic signal sequence (1-4). These isoforms have different expression patterns, subcellular localization, and function. The membrane-bound long form of human IL-17RD is synthesized as a 739 amino acid (aa) precursor protein with a putative 27 aa signal peptide, a 272 aa extracellular domain, a 20 aa transmembrane segment and a 420 aa cytoplastic domain. The extracellular domain contains one Ig-like domain and a fibronectin type III motif. The cytoplasmic domain shares homology with the intracellular domains of IL-17 receptor family members and shows one TIR (Toll/IL-1 Receptor) domain and a putative TRAF6-binding motif (2). Natural IL-17 RD has been shown to form homomultimeric complexes (3). Unlike the alternate splice form of IL-17 RD that has a restricted pattern of expression, the full-length IL-17 RD isoform is expressed in most adult tissues and during embryonic development (3, 5). Functionally, IL-17 RD has been shown to be an inhibitor of FGF signaling. The molecule’s extracellular domain does not seem to be involved. There is an interaction between the intracellular domains of FGFR1/2 and IL-17 RD that blocks ERK dissociation from MEK, thereby interfering with downstream ERK activation of nuclear Elk-1 (8). IL-17 RD has also been reported to interact with TAK1 and induce JNK activation and apoptosis (9). Ligands that interact with the extracellular domain of IL-17 RD have not been identified.