IL-6R alpha 蛋白, Human (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]. IL-6R alpha/CD126, Human consists of 468 amino acids (M1-R468) with two fibronectin type-III-like domains contained in the N-terminal part (113-217 a.a, 218-316 a.a), and a soluble form (1-365 a.a). Soluble IL-6R (sIL-6R) binds IL-6 and dimerized gp130 to achieve trans signaling, and exhibits a tissue expression property in some immune systems. IL-6R alpha Protein, Human (M1-P365) is soluble form and produced in HEK293 cells with a C-Terminal hFc-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]。
人类 IL-6R α 蛋白的氨基酸序列差异很大来自小鼠 (54.07%) 和大鼠 (54.68%)。
IL-6R α 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，有潜力通过树突状细胞^[4]的“簇信号传导”将幼稚 CD4⁺ T 细胞驱动至 Th17 谱系。
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-6R α (IL-6Rα) 上裂解下来，并作为 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 regulates IL-6 (1^-6-1³ ng/mL; 6 min at least) and triggers chemokinesis of tissue mast cells of rats^[1].
sIL-6R (1 ng/mL; 48 h) shows no effect on adhesion molecules VCAM-1 and ICAM-1, but potently inhibits TNF-α induced VCAM-1 expression but not ICAM-1, by being combined with IL-6 (5 ng/mL) in U373-MG human astroglioma cells^[2].
sIL-6R (1 ng/mL; 3 min) induce tyrosine phosphorylation of STAT-3 in U373-MG astroglioma cells and human astrocytes^[2].
IL-6/sIL-6R complex (1 ng/mL; 24 h) induces NF-κB and STAT3 activation and Bcl-2 expression for human fibroblast-like synoviocytes in rheumatoid arthriti^[3].

IL-6R alpha exerts negative regulation on MAO-A activity to release angiogenic and invasive features of breast cancer cells from MAO-A inhibition^[4].
sIL-6R (human), combinded with IL-6 (human), coexpressing in double-transgenic mice, inhibits mice growth and causes an extreme expansion of extramedullary hematopoietic progenitor cells compared with human IL-6 and human sIL-6R single-transgenic mice^[5].
sIL-6R acts as a serum-binding protein for IL-6 and prolongs the plasma half life of IL-6^[6].

Measured in a cell proliferation assay using TF-1 human erythroleukemic cells. The ED₅₀ for this effect is 4.366 ng/mL in the presence of 2 ng/mL recombinant mouse IL-6, corresponding to a specific activity is 2.29×10^5 units/mg.

• 
  Measured in a cell proliferation assay using TF-1 human erythroleukemic cells. The ED₅₀ for this effect is 4.366 ng/mL in the presence of 2 ng/mL recombinant mouse IL-6, corresponding to a specific activity is 2.29×10⁵ units/mg.

Human

HEK293

C-hFc

P08887-1/NP_000556.1 (L20-P365)

3570  [NCBI]

LAPRRCPAQEVARGVLTSLPGDSVTLTCPGVEPEDNATVHWVLRKPAAGSHPSRWAGMGRRLLLRSVQLHDSGNYSCYRAGRPAGTVHLLVDVPPEEPQLSCFRKSPLSNVVCEWGPRSTPSLTTKAVLLVRKFQNSPAEDFQEPCQYSQESQKFSCQLAVPEGDSSFYIVSMCVASSVGSKFSKTQTFQGCGILQPDPPANITVTAVARNPRWLSVTWQDPHSWNSSFYRLRFELRYRAERSKTFTTWMVKDLQHHCVIHDAWSGLRHVVQLRAQEEFGQGEWSEWSPEAMGTPWTESRSPPAENEVSTPMQALTTNKDDDNILFRDSANATSLPVQDSSSVPLP

80-100 kDa

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

无菌粉末.

Lyophilized from a 0.2 μm filtered solution of 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.

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]. Misiak-Tłoczek A, et al. IL-6, but not IL-4, stimulates chemokinesis and TNF stimulates chemotaxis of tissue mast cells: involvement of both mitogen-activated protein kinases and phosphatidylinositol 3-kinase signalling pathways. APMIS. 2009 Aug;117(8):558-67.  [Content Brief]

  [10]. Oh JW, et al. Role of IL-6 and the soluble IL-6 receptor in inhibition of VCAM-1 gene expression. J Immunol. 1998 Nov 1;161(9):4992-9.  [Content Brief]

  [11]. Kim SK, et al. Melittin enhances apoptosis through suppression of IL-6/sIL-6R complex-induced NF-κB and STAT3 activation and Bcl-2 expression for human fibroblast-like synoviocytes in rheumatoid arthritis. Joint Bone Spine. 2011 Oct;78(5):471-7.  [Content Brief]

  [12]. Bharti R, Dey G, Das AK, Mandal M. Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer. Br J Cancer. 2018 May;118(11):1442-1452.  [Content Brief]

  [13]. Malte Peters, et al. Extramedullary Expansion of Hematopoietic Progenitor Cells in Interleukin (IL)-6–sIL-6R Double Transgenic Mice. J Exp Med (1997) 185 (4): 755-766.

  [14]. Fattori E, et al. Development of progressive kidney damage and myeloma kidney in interleukin-6 transgenic mice. Blood. 1994 May 1;83(9):2570-9.  [Content Brief]