IL6R - Interleukin 6 Receptor | Elisa - Clia - Antibody - Protein

Background:

IL6R is found on the surface of many types of cells, including immune cells like T cells, B cells, and macrophages, as well as non-immune cells like hepatocytes (liver cells) and endothelial cells (cells lining blood vessels).The IL6R is a transmembrane glycoprotein composed a extracellular Domain that contains the binding site for interleukin-6 (IL-6). It consists of two cytokine receptor homology domains (CRH1 and CRH2) responsible for IL-6 binding.A transmembrane Domain Anchoring the receptor in the cell membrane, And a Intracellular Domain Involved in signal transduction upon IL-6 binding, initiating downstream signaling cascades. The IL6R mediates the biological effects of IL-6 by binding to it and initiating intracellular signaling pathways. Upon IL-6 binding, the IL6R undergoes conformational changes that lead to the recruitment of a co-receptor called gp130, forming a functional signaling complex. This complex activates various downstream signaling pathways, including the Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway, the mitogen-activated protein kinase (MAPK) pathway, and the phosphatidylinositol 3-kinase (PI3K) pathway.The signaling initiated by IL-6 through its receptor is involved in numerous physiological processes, including: Regulation of immune responses, Hematopoiesis,Metabolic regulation,Neural development.

Protein Structure:

IL6R is a type I membrane glycoprotein that consists of two main forms: a membrane-bound form (mIL6R) and a soluble form (sIL6R). The membrane-bound IL6R is composed of three main domains:

• Extracellular domain: Contains the IL-6 binding site.
• Transmembrane domain: Anchors the receptor to the cell membrane.
• Intracellular domain: Involved in signal transduction.

The soluble form (sIL6R) arises from proteolytic cleavage of the membrane-bound receptor or through alternative splicing of IL6R mRNA. Both forms can bind IL-6, but their roles in signaling differ.

Classification and Subtypes:

IL6R is classified under the cytokine receptor superfamily, particularly the IL-6 receptor family. This family also includes receptors for other cytokines such as IL-11, IL-27, and leukemia inhibitory factor (LIF). The receptor family is characterized by their association with the glycoprotein 130 (gp130) signal-transducing subunit.

Function and Biological Significance:

IL6R mediates the effects of IL-6 through its interaction with gp130, which is ubiquitously expressed on cell surfaces. The IL-6/IL6R/gp130 complex triggers intracellular signaling cascades, including:

• JAK/STAT Pathway: Activation of Janus kinases (JAKs) and subsequent phosphorylation of signal transducer and activator of transcription (STAT) proteins, leading to gene transcription.
• MAPK Pathway: Mitogen-activated protein kinases (MAPKs) activation, involved in cell growth, differentiation, and survival.
• PI3K/Akt Pathway: Phosphoinositide 3-kinase (PI3K) and Akt activation, contributing to cell survival and metabolism.

IL6R signaling is involved in:

• Immune Response: Modulating T-cell and B-cell differentiation and proliferation.
• Inflammation: Inducing the production of acute-phase proteins and mediating inflammatory responses.
• Hematopoiesis: Supporting the growth and differentiation of hematopoietic stem cells.

Interactions:

• IL-6: Binds to both mIL6R and sIL6R, forming a complex that interacts with gp130 to initiate signaling.
• gp130: A signal-transducing subunit essential for IL-6R-mediated signal transduction. Upon IL-6 binding, gp130 dimerizes and activates intracellular signaling pathways.
• Proteases: Enzymes that cleave mIL6R to generate sIL6R, modulating the extent and range of IL-6 signaling.

Clinical Issues:

• Inflammatory Diseases: Dysregulated IL6R signaling is implicated in autoimmune and inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease.
• Cancer: Aberrant IL6R/IL-6 signaling contributes to cancer progression by promoting tumor growth, survival, and metastasis. Elevated levels of IL6R and IL-6 are associated with poor prognosis in various cancers.
• Therapeutic Target: IL6R is a therapeutic target for treating inflammatory diseases and certain cancers. Tocilizumab, a monoclonal antibody against IL6R, is approved for treating rheumatoid arthritis and other inflammatory conditions. Other IL6R inhibitors are under investigation for their potential in cancer therapy.

Summary:

Interleukin 6 receptor (IL6R) is a critical component of the IL-6 signaling pathway, playing a significant role in immune response, inflammation, and hematopoiesis. It exists in both membrane-bound and soluble forms, each contributing differently to IL-6 signaling. Dysregulated IL6R signaling is linked to various inflammatory diseases and cancers, making it a valuable therapeutic target. Understanding IL6R's structure, function, and interactions is essential for developing effective treatments for conditions associated with abnormal IL-6 signaling.