IL-6R Protein, Rat (HEK293, Fc)

IL-6R alpha is a subunit alpha of IL-6 receptors, also shared by other interleukin receptors. IL-6R alpha acts as IL-6 agonist and involves in JAK/STAT, MAPK, and Akt signaling pathway^[1][2]. with a fibronectin type-III-like domain contained in the N-terminal part and a transmembrane domain. Soluble IL-6R (sIL-6R) interacts with SORL1 to conduct internalization and binds IL-6 and dimerized gp130 to deliver trans signalin. IL-6R alpha, Rat is soluble form and produced in HEK293 cells with a C-Terminal hFc-tag.

IL-6 acts as both inflammatory factor and anti-inflammatory factor, fuels cancer progression through activating a series of downstream signalling cascade including gp130 (dimers), JAK/STAT, MAPK, and Akt^[1][2].
IL-6R alpha (IL-6Rα) as a part of the receptor for interleukin 6, is a type I transmembrane glycoprotein, which forms a complex with the type I transmembrane signal transducer Glycoprotein 130 (CD130) and regulates the biological activity of IL-6 with a low affinity^[3].
The sequence of amino acids in IL-6R alpha proteins of rat is very different from human (54.68%), but shows high similarity with mouse (89.3%).
IL-6R alpha has 2 isoform including mIL6R (the longer one) or sIL6R (the shorter one):
The mIL6R is membrane-bound interleukin-6 receptor, has the potential to drive naive CD4⁺ T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells^[4].
The sIL-6R is soluble interleukin-6 receptor subunit, cleaved from IL-6R alpha (IL-6Rα) in activated CD4⁺ T cells by proteolysis, and serves as IL-6 agonist. sIL-6R binds membrane-bound IL6R and subunit IL6ST to activate regenerative and anti-inflammatory signal via IL-6 trans signaling and promotes pro-inflammatory properties of IL-6. The hydrolysis of IL-6R alpha is also called ectodomain shedding^[1].
IL-6R alpha involves in regulating cell growth and differentiation, and plays an important role in regulation of immune response, acute-phase reactions and hematopoiesis^[5].
However, IL-6R alpha shows tissue expression specificity in liver and some cells of the immune system, thus results a limitation of IL6 signaling^[6].
It's worth noting that IL-6R alpha dysregulation is implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases, and prostate cancer^[7][8].

IL-6R alpha (sIL-6R) (1 ng/mL; 24 h) induces MMP-2 activity in rheumatoid arthritis (RA) synovial fibroblasts further 2-fold, which is involved in joint destruction in rheumatoid arthritis (RA) rats^[1].
IL-6R alpha (sIL-6R) (125 ng/mL; 2-48 h) increases the mRNA level of IL-6 in primary rat osteoblasts (Ob cells), and also stimulates IL-6 xogenous added to increase the level of IL-6 mRNA in cells^[2].

Rat

HEK293

C-hFc

NP_058716.2 (L20-P364)

24499  [NCBI]

Approximately 64.8 kDa

Greater than 90% as determined by reducing SDS-PAGE.

<1 EU/μg, determined by LAL method.

• [1]. Garbers C, et al. Inhibition of classic signaling is a novel function of soluble glycoprotein 130 (sgp130), which is controlled by the ratio of interleukin 6 and soluble interleukin 6 receptor. J Biol Chem. 2011 Dec 16;286(50):42959-70.  [Content Brief]

  [2]. Malemud, et al. Defective JAK-STAT Pathway Signaling Contributes to Autoimmune Diseases. Curr Pharmacol Rep 4, 358-366.

  [3]. Larsen JV, et al. SorLA in Interleukin-6 Signaling and Turnover. Mol Cell Biol. 2017 May 16;37(11):e00641-16.  [Content Brief]

  [4]. Kang S, et al. Targeting Interleukin-6 Signaling in Clinic. Immunity. 2019 Apr 16;50(4):1007-1023.  [Content Brief]

  [5]. Giannitrapani L, et al. Circulating IL-6 and sIL-6R in patients with hepatocellular carcinoma. Ann N Y Acad Sci. 2002 Jun;963:46-52.  [Content Brief]

  [6]. Arnold P, et al. Joint Reconstituted Signaling of the IL-6 Receptor via Extracellular Vesicles. Cells. 2020 May 24;9(5):1307.  [Content Brief]

  [7]. Mishra AK, et al. Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells. Leukemia. 2019 Nov;33(11):2695-2709.  [Content Brief]

  [8]. Gruber CN, et al. Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C). Cell. 2020 Nov 12;183(4):982-995.e14.  [Content Brief]

  [9]. Ahmed S, et al. Epigallocatechin-3-gallate inhibits IL-6 synthesis and suppresses transsignaling by enhancing soluble gp130 production. Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14692-7.  [Content Brief]

  [10]. Franchimont N, Rydziel S, Canalis E. Interleukin 6 is autoregulated by transcriptional mechanisms in cultures of rat osteoblastic cells. J Clin Invest. 1997 Oct 1;100(7):1797-803.  [Content Brief]