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IL-6R alpha Protein, Human (CHO)

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Based on 2 publication(s) in Google Scholar

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. 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 (L20-P365) is soluble form and expressed by CHO cells with a full length of the sequence of 346 amino acids.

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  • Species: Human
  • Source: CHO
  • Storage:
    Stored at -20°C for 2 years from date of receipt. 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.
  • Experimental Validation Results for IL-6R alpha Protein, Human (CHO)
  • Experimental Validation Results for IL-6R alpha Protein, Human (CHO)
  • IL-6R alpha Protein, Human (CHO) Product Image
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  • Biological Activity
  • Technical Parameters
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Biological Activity

Description

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 (L20-P365) is soluble form and expressed by CHO cells with a full length of the sequence of 346 amino acids.

Background

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 human is very different from mouse (54.07%) and rat (54.68%).
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].

In Vitro

IL-6R alpha regulates IL-6 (10-6-103 ng/mL; 60 min at least) and triggers chemokinesis of tissue mast cells of rats[1].
sIL-6R (100 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 (100 ng/mL; 30 min) induce tyrosine phosphorylation of STAT-3 in U373-MG astroglioma cells and human astrocytes[2].
IL-6/sIL-6R complex (100 ng/mL; 24 h) induces NF-κB and STAT3 activation and Bcl-2 expression for human fibroblast-like synoviocytes in rheumatoid arthriti[3].

In Vivo

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].

Verified Bioactivity

1. The ED50 is <0.2 μg/mL as measured by M1 cells.
2. Measured in a cell proliferation assay using TF-1 human erythroleukemic cells. The ED50 for this effect is 0.2113 ng/mL in the presence of 2 ng/mL recombinant mouse IL-6, corresponding to a specific activity is 4.73×106 units/mg.

MCE Validation Data

  • Purity - SDS-PAGE

    Purity - SDS-PAGE

    ≥ 95%, as determined by reducing SDS-PAGE.

  • Bioactivity - Cell-Based Assay

    Bioactivity - Cell-Based Assay

    Measured in a cell proliferation assay using TF-1 human erythroleukemic cells. The ED50 for this effect is 0.2113 ng/mL in the presence of 2 ng/mL recombinant mouse IL-6, corresponding to a specific activity is 4.73×106units/mg.

Technical Parameters

  • Species Human
  • Source CHO
  • Tag Tag Free
  • Accession

    P08887-1 (L20-P365)

  • Gene ID
    3570  [NCBI]
  • Molecular Construction
    • N-term
    • IL-6Rα (L20-P365)
      Accession # P08887-1
    • C-term
  • Protein Length

    Extracellular Domain

  • Synonyms

    IL6R; IL-6R 1; Interleukin 6 Receptor; IL-6RA; Gp80; Interleukin 6 Receptor Subunit Alpha; Interleukin-6 Receptor Subunit Alpha; IL-6R Subunit Alpha; Membrane Glycoprotein 80; IL-6R-Alpha; IL-1Ra; IL-6R-1; IL6RA; IL6QTL; IL-6R; IL6RQ; CD126; HIES5; IL-6 Receptor Subunit Alpha; IL6Q; CD126 Antigen

  • AA Sequence

    LAPRRCPAQEVARGVLTSLPGDSVTLTCPGVEPEDNATVHWVLRKPAAGSHPSRWAGMGRRLLLRSVQLHDSGNYSCYRAGRPAGTVHLLVDVPPEEPQLSCFRKSPLSNVVCEWGPRSTPSLTTKAVLLVRKFQNSPAEDFQEPCQYSQESQKFSCQLAVPEGDSSFYIVSMCVASSVGSKFSKTQTFQGCGILQPDPPANITVTAVARNPRWLSVTWQDPHSWNSSFYRLRFELRYRAERSKTFTTWMVKDLQHHCVIHDAWSGLRHVVQLRAQEEFGQGEWSEWSPEAMGTPWTESRSPPAENEVSTPMQALTTNKDDDNILFRDSANATSLPVQDSSSVPLP

  • Molecular Weight

    Approximately 50-70 kDa, based on SDS-PAGE under reducing conditions, due to the glycosylation.

  • Glycosylation

    Yes

  • Purity

    ≥ 95%, as determined by reducing SDS-PAGE.

Product Properties

Appearance

Lyophilized powder.

Formulation

1.Lyophilized from a 0.22 μm filtered solution of PBS.
2.Lyophilized from a 0.22 μm filtered solution of 20 mM PB, 150 mM NaCl, pH 7.4.
Please refer to the lot-specific COA for specific buffer information.

Endotoxin Level

<0.2 EU/μg, determined by LAL method.

Reconstitution

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).

Storage & Stability

Stored at -20°C for 2 years from date of receipt. 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.

Shipping

Room temperature in continental US; may vary elsewhere.

References

[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]

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The Specific Activity Calculator Equation
  • Specific Activity (Unit/mg)
  • Biological Activity (ED50)

Specific Activity (Unit/mg) = 106 ÷ Biological Activity (ED50)

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100 mg

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Measured by its ability to inhibit anti-CD3-induced proliferation of stimulated CTLL-2 mouse cytotoxic T cells. The ED50 this effect is 0.8023 μg/ml, corresponding to a specific activity is 1246.42 units/mg.

Assay Types
  • 1/16

    MedChemExpress Validation
     ≥ 95%, as determined by reducing SDS-PAGE.

  • 1/16

    MedChemExpress Validation
     Measured in a cell proliferation assay using TF-1 human erythroleukemic cells. The ED50 for this effect is 0.2113 ng/mL in the presence of 2 ng/mL recombinant mouse IL-6, corresponding to a specific activity is 4.73×106units/mg.

  • IL-6R alpha Protein, Human (CHO) Product Image
    1/16
  • Experimental Validation Results for IL-6R alpha Protein, Human (CHO)
  • Experimental Validation Results for IL-6R alpha Protein, Human (CHO)
  • IL-6R alpha Protein, Human (CHO) Product Image