IL-6R alpha Protein, Mouse (HEK293, His)

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]. IL-6R alpha, Mouse consists of 460 amino acids (M1-R460) with two fibronectin type-III-like domains contained in the N-terminal part (109-214 a.a, 215-313 a.a). Soluble IL-6R (sIL-6R) can be detected in the cerebrospinal fluid, conducts trans signaling by binding IL-6 and dimerized gp130, and exhibits a immune tissue expression property. IL-6R alpha Protein, Mouse (HEK293, His) is soluble form and produced in HEK293 cells with a C-Terminal His-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 mouse is very different from human (54.07%), but shows high similarity with rat (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 (mSR323) (10 ng/mL; 60 min; room temperature) binds MR16-1, the IL-6R antibody, with the N-terminal half of the fibronectin domain II in COS-7 cells^[1].

sIL-6R (mIL-6R α) achieves accelerated regeneration of the axotomized nerve in transgenic mice constitutively expressing both IL-6 and IL-6R, compared with nontransgenic controls^[2].
IL-6 signal may play an important role in nerve regeneration after trauma in vivo^[2].
sIL-6R (mIL-6R α), causes nodular regenerative hyperplasia and adenomas of the liver in over-expressing double IL-6/sIL-6R transgenic mice^[3].

Measured in a cell proliferation assay using TF-1 human erythroleukemic cells. The ED₅₀ for this effect is 3.014 ng/mL in the presence of 2 ng/mL recombinant mouse IL-6, corresponding to a specific activity is 3.32×10⁵ units/mg.

• 
  Measured in a cell proliferation assay using TF-1 human erythroleukemic cells. The ED₅₀ for this effect is 3.014 ng/mL in the presence of 2 ng/mL recombinant mouse IL-6, corresponding to a specific activity is 3.32×10⁵ units/mg.

Mouse

HEK293

C-6*His

P22272 (L20-P364)

16194  [NCBI]

LVLGSCRALEVANGTVTSLPGATVTLICPGKEAAGNVTIHWVYSGSQNREWTTTGNTLVLRDVQLSDTGDYLCSLNDHLVGTVPLLVDVPPEEPKLSCFRKNPLVNAICEWRPSSTPSPTTKAVLFAKKINTTNGKSDFQVPCQYSQQLKSFSCQVEILEGDKVYHIVSLCVANSVGSKSSHNEAFHSLKMVQPDPPANLVVSAIPGRPRWLKVSWQHPETWDPSYYLLQFQLRYRPVWSKEFTVLLLPVAQYQCVIHDALRGVKHVVQVRGKEELDLGQWSEWSPEVTGTPWIAEPRTTPAGILWNPTQVSVEDSANHEDQYESSTEATSVLAPVQESSSMSLP

approximately 50-65 kDa

• 
  Greater than 95% as determined by reducing SDS-PAGE.

Lyophilized powder.

Lyophilized from a 0.2 μm filtered solution of PBS, pH 7.4 or 20 mM PB, 150 mM NaCl, pH 7.4.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O. For long term storage it is recommended to add a carrier protein (0.1% BSA, 5% HSA, 10% FBS or 5% Trehalose).

Stored at -20°C for 2 years. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [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]. Okazaki M, et al. Characterization of anti-mouse interleukin-6 receptor antibody. Immunol Lett. 2002 Dec 3;84(3):231-40.  [Content Brief]

  [10]. Hirota H, Kiyama H, Kishimoto T, Taga T. Accelerated Nerve Regeneration in Mice by upregulated expression of interleukin (IL) 6 and IL-6 receptor after trauma. J Exp Med. 1996 Jun 1;183(6):2627-34.  [Content Brief]

  [11]. Maione D, et al. Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver. EMBO J. 1998 Oct 1;17(19):5588-97.  [Content Brief]