IL-6R 蛋白, Rat (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, Rat consists of 462 amino acids (M1-R462) with a fibronectin type-III-like domain contained in the N-terminal part (215-313 a.a) and a transmembrane domain (365-385 a.a). 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 (I44-E357) is soluble form and produced in HEK293 cells with a C-Terminal His-tag.

IL-6 兼具炎症因子和抗炎因子的作用，通过激活一系列下游信号级联反应，包括 gp130（二聚体）、JAK/STAT、MAPK 和 Akt^[1]< super>[2]。
IL-6R α (IL-6Rα) 作为白细胞介素 6 受体的一部分，是一种 I 型跨膜糖蛋白，与 I 型跨膜信号形成复合物转导糖蛋白 130 (CD130) 并以低亲和力调节 IL-6 的生物活性^[3]。
大鼠 IL-6R α 蛋白的氨基酸序列差异很大来自人类 (54.68%)，但与小鼠 (89.3%) 相似。
IL-6R alpha 有 2 个亚型，包括 mIL6R（较长的一个）或 sIL6R（较短的一个）：
mIL6R是膜结合白细胞介素 6 受体，具有通过树突状细胞^[4]的“簇信号传导”将幼稚 CD4⁺ T 细胞驱动至 Th17 谱系的潜力。
sIL-6R是可溶性白细胞介素6受体亚基，通过蛋白水解作用从活化的CD4⁺ T细胞中的IL-6Rα（IL-6Rα）上裂解下来，作为IL-6激动剂。sIL-6R 结合膜结合的 IL6R 和亚基 IL6ST，通过 IL-6 反式信号传导激活再生和抗炎信号，并促进 IL-6 的促炎特性。IL-6R α 的水解也称为胞外域脱落^[1]。
IL-6R α 参与调节细胞生长和分化，在免疫反应调节中发挥重要作用。急性期反应和造血^[5]。
然而，IL-6R α 在肝脏和免疫系统的一些细胞中表现出组织表达特异性，从而导致 IL6 信号传导受到限制^[6]。
值得注意的是，IL-6R α 失调与多种疾病的发病机制有关，例如多发性骨髓瘤、自身免疫性疾病和前列腺癌^[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].

Measured by its binding ability in a functional ELISA. When Human IL-6 is immobilized at 0.25 µg/mL (100 µL/ well) can bind Biotinylated Recombinant Rat IL-6R alpha. The ED₅₀ for this effect is 1.077 μg/mL.

Rat

HEK293

C-His

NP_058716.2 (L20-P364)

24499  [NCBI]

LVLGSCRALEVANGTVTSLPGATVTLICPGKEAAGNATIHWVYSGSQSREWTTTGNTLVLRAVQVNDTGHYLCFLDDHLVGTVPLLVDVPPEEPKLSCFRKNPLVNAFCEWHPSSTPSPTTKAVMFAKKINTTNGKSDFQVPCQYSQQLKSFSCEVEILEGDKVYHIVSLCVANSVGSRSSHNVVFQSLKMVQPDPPANLVVSAIPGRPRWLKVSWQDPESWDPSYYLLQFELRYRPVWSKTFTVWPLQVAQHQCVIHDALRGVKHVVQVRGKEEFDIGQWSKWSPEVTGTPWLAEPRTTPAGIPGNPTQVSVEDYDNHEDQYGSSTEATSVLAPVQGSSPIPLP

Approximately 50-70 kDa

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

无菌粉末

Lyophilized from a 0.2 μm filtered solution of PBS, pH 7.4. Normally 5 % - 8 % trehalose, mannitol and 0.01% Tween 80 are added as protectants before lyophilization.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O.

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.

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  [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]