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  6. IL-6R alpha Protein, Human (HEK293, Fc)

IL-6R alpha Protein, Human (HEK293, Fc)

Cat. No.: HY-P73222
COA Handling Instructions

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 (M1-P365) is soluble form and produced in HEK293 cells with a C-Terminal hFc-tag.

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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 (M1-P365) is soluble form and produced in HEK293 cells with a C-Terminal hFc-tag.

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 (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].

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].

Biological Activity

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.
Species

Human

Source

HEK293

Tag

C-hFc

Accession

NP_000556.1 (L20-P365)

Gene ID
Molecular Construction
N-term
IL-6Rα (L20-P365)
Accession # NP_000556.1
hFc
C-term
Synonyms
Interleukin-6 receptor subunit alpha; IL-6R-alpha; IL-6R 1; gp80; CD126
AA Sequence

LAPRRCPAQEVARGVLTSLPGDSVTLTCPGVEPEDNATVHWVLRKPAAGSHPSRWAGMGRRLLLRSVQLHDSGNYSCYRAGRPAGTVHLLVDVPPEEPQLSCFRKSPLSNVVCEWGPRSTPSLTTKAVLLVRKFQNSPAEDFQEPCQYSQESQKFSCQLAVPEGDSSFYIVSMCVASSVGSKFSKTQTFQGCGILQPDPPANITVTAVARNPRWLSVTWQDPHSWNSSFYRLRFELRYRAERSKTFTTWMVKDLQHHCVIHDAWSGLRHVVQLRAQEEFGQGEWSEWSPEAMGTPWTESRSPPAENEVSTPMQALTTNKDDDNILFRDSANATSLPVQDSSSVPLP

Molecular Weight

80-100 kDa

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

Lyophilized powder.

Formulation

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

Endotoxin Level

<1 EU/μg, determined by LAL method.

Reconstitution

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

Storage & Stability

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.

Shipping

Room temperature in continental US; may vary elsewhere.

Documentation
References
Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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The reconstitution calculator equation

Volume (to add to vial) = Mass (in vial) ÷ Desired Reconstitution Concentration

Volume (to add to vial) = Mass (in vial) ÷ Desired Reconstitution Concentration
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The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
× = ×
C1   V1   C2   V2

The specific activity calculator equation

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

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

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IL-6R alpha Protein, Human (HEK293, Fc)
Cat. No.:
HY-P73222
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