IL-6 Family
Available Resources for the Study of IL-6 Family
At Creative BioMart, our primary dedication revolves around advancing research in the domain of the IL-6 family. With unwavering commitment, we strive to provide scientists with state-of-the-art tools and expertise related to IL-6 family receptors, ligands, and signaling molecules.
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- Moreover, we provide a wealth of valuable resources to support research efforts within the IL-6 family. These resources cover pathways, protein functions, interacting proteins, and other pertinent information, significantly enhancing research outcomes and impact.
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About IL-6 Family
The IL-6 family of cytokines is a group of proteins that play critical roles in immune regulation, inflammation, and various physiological processes. This family consists of several ligands, receptors, and related signaling molecules. Here is an introduction to some key members of the IL-6 family:
Ligands
The ligands within the IL-6 family are cytokines that bind to specific receptors and initiate signaling cascades. Some important ligands include:
- Interleukin-6 (IL-6): IL-6 is a multifunctional cytokine involved in immune responses, inflammation, and hematopoiesis. It is produced by multiple cell types, including immune cells, fibroblasts, and endothelial cells. IL-6 acts through both classic signaling, which involves binding to the membrane-bound IL-6 receptor (mIL-6R), and trans-signaling, which occurs when IL-6 forms a complex with soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (gp130).
- Interleukin-11 (IL-11): IL-11 is primarily produced by stromal cells and plays roles in hematopoiesis, bone metabolism, and gastrointestinal mucosal protection. It signals through a receptor complex composed of IL-11 receptor alpha (IL-11Rα) and gp130.
- Oncostatin M (OSM): OSM is produced by activated T cells and macrophages and is involved in inflammation, tissue remodeling, and hematopoiesis. OSM signals through a receptor complex consisting of OSM receptor (OSMR) and gp130.
- Leukemia Inhibitory Factor (LIF): LIF is produced by various cell types and participates in embryonic development, stem cell maintenance, and acute-phase response. LIF signals through a receptor complex composed of LIF receptor (LIFR) and gp130.
Receptors
The IL-6 family of cytokines utilizes specific receptors to transmit signals. The primary receptor subunits include:
- IL-6 Receptor (IL-6R): IL-6R is a glycoprotein expressed on the surface of various cell types. It can exist in both membrane-bound (mIL-6R) and soluble forms (sIL-6R). IL-6 binds to mIL-6R to initiate classic signaling, while the sIL-6R can bind IL-6 and form a complex with gp130, enabling trans-signaling in cells that lack mIL-6R.
- IL-11 Receptor Alpha (IL-11Rα): IL-11Rα is the specific receptor subunit for IL-11. It forms a complex with gp130 to transduce IL-11 signaling.
- OSM Receptor (OSMR): OSMR is responsible for binding OSM. It pairs with gp130 to activate downstream signaling pathways.
- LIF Receptor (LIFR): LIFR is the receptor subunit for LIF. It forms a complex with gp130 to transduce LIF signaling.
Signaling Molecules
The IL-6 family of cytokines utilizes shared intracellular signaling molecules to transmit signals. These include:
- Glycoprotein 130 (gp130): gp130 is a common signaling subunit shared by all members of the IL-6 family. It is necessary for signal transduction upon ligand binding to their respective receptors. gp130 activation leads to the recruitment and phosphorylation of Janus kinases (JAKs) and subsequent activation of downstream signaling pathways, such as the JAK-STAT pathway, MAPK pathway, and PI3K/Akt pathway.
- Janus Kinases (JAKs): JAKs, particularly JAK1 and JAK2, are associated with the cytoplasmic domain of the IL-6 receptor complex. Upon ligand binding and receptor activation, JAKs are activated and phosphorylate specific tyrosine residues on the receptor and themselves, initiating downstream signaling cascades.
- Signal Transducer and Activator of Transcription (STAT) Proteins: The activated IL-6 receptor complex recruits and phosphorylates STAT proteins, primarily STAT3. Phosphorylated STAT3 forms dimers and translocates to the nucleus, where it regulates the transcription of target genes involved in various cellular processes.
The IL-6 family of cytokines, their receptors, and signaling molecules collectively contribute to the regulation of immune responses, inflammation, and various physiological functions. Understanding the interactions within this family provides insights into the complex signaling networks and potential therapeutic targets for various diseases associated with dysregulated IL-6 family signaling.
Fig.1 Receptor usage of IL-6 family cytokines. (West NR, 2019)
Signaling Molecules and Pathways
Activation of IL-6 family receptors leads to the activation of specific signaling pathways involving various molecules:
- Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) Pathway: Upon ligand binding, the associated receptor complex activates JAKs, which phosphorylate and activate STAT proteins. The activated STAT proteins translocate to the nucleus and regulate gene expression.
- Mitogen-Activated Protein Kinase (MAPK) Pathway: The IL-6 family cytokines can activate MAPK pathways, including extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase (JNK). These pathways regulate cell proliferation, survival, and inflammation.
Fig.2 The role of IL-6/STAT3 signaling pathway and interactions with other pathways in hepatocarcinogenesis. (Jin K, et al., 2017)
Creative BioMart is committed to helping you achieve your scientific goals and make meaningful contributions to the study of the mechanisms of action of the various components of the IL-6 family and their role in disease. Contact us today to learn more about our products and resources.
Related References:
- West NR. Coordination of immune-stroma crosstalk by IL-6 family cytokines. Front Immunol. 2019;10:1093. Published 2019 May 15.
- Jin K, Li T, Sánchez-Duffhues G, Zhou F, Zhang L. Involvement of inflammation and its related microRNAs in hepatocellular carcinoma. Oncotarget. 2017;8(13):22145-22165. doi:10.18632/oncotarget.13530
