IL-1 Family Signaling Molecules
Available Resources for IL-1 Family Signaling Molecules Research
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In addition to our extensive product offering, we also provide a wealth of information on IL-1 family signaling molecules. Our resources cover a range of topics including pathways, protein function, interacting proteins, related articles, and research areas. These resources serve as valuable references for researchers seeking to deepen their understanding of IL-1 family signaling molecules and their role in physiological processes. By offering both products and knowledge, we are dedicated to supporting researchers and driving advancements in this research field.
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About IL-1 Family Signaling Molecules
IL-1 family signaling molecules encompass a group of cytokines, receptors, and intracellular signaling components that are involved in immune responses, inflammation, and various physiological processes. Let's take a closer look at each category:
IκB Kinases
CHUK (IKKα) and IKBKE (IKKε): These are IκB kinases that phosphorylate inhibitor of kappa-B (IκB) proteins. This phosphorylation leads to the degradation of IκB and subsequent activation of nuclear factor kappa-B (NF-κB) transcription factors. IKKα and IKKε play crucial roles in the regulation of NF-κB signaling pathway.
Transcription Factors
FOS: FOS is a proto-oncogene that encodes the c-Fos protein. It forms a heterodimeric complex with c-Jun, another transcription factor, to create the transcription factor complex AP-1 (Activator Protein-1). AP-1 regulates gene expression in response to various stimuli, including IL-1.
Inhibitors of NF-κB
NFKBIB (IκBβ): NFKBIB is an inhibitor of NF-κB subunit beta. It binds to NF-κB and sequesters it in the cytoplasm, preventing its translocation into the nucleus and subsequent gene activation.
IL-1 Receptor-Associated Kinases (IRAKs)
IRAK2 and IRAK4: These are IL-1 receptor-associated kinases that play essential roles in IL-1 receptor signaling. They phosphorylate downstream signaling molecules, leading to the activation of NF-κB and MAPK pathways. IRAK2 and IRAK4 are critical components in IL-1-mediated immune responses.
MAPK Kinases (MKKs)
MAP2K3 (MKK3), MAP2K4 (MKK4), and MKK6: These are members of the mitogen-activated protein kinase kinase (MAPKK) family. They phosphorylate and activate stress-activated protein kinases, such as c-Jun N-terminal kinases (JNKs) and p38 MAPKs. These MAPK pathways are involved in IL-1 signaling and regulate cellular responses to stress and inflammation.
MAP3K
MAP3K7 (TAK1): MAP3K7, also known as TGF-β-activated kinase 1 (TAK1), is a mitogen-activated protein kinase kinase kinase (MAP3K) involved in IL-1 signaling. It phosphorylates and activates downstream components, including IKK complex and MAPKs, to transmit IL-1 signals and regulate cellular responses.
Extracellular Signal-Regulated Kinases (ERKs)
ERK1 (MAPK3) and ERK2 (MAPK1): ERK1 and ERK2 are members of the extracellular signal-regulated kinase (ERK) family. They are activated by IL-1 and other growth factors, regulating gene expression and cellular processes such as proliferation and differentiation.
c-Jun N-terminal Kinases (JNKs)
JNK2 (MAPK9) and MAPK8 (JNK1): JNK2 and MAPK8 are members of the c-Jun N-terminal kinase (JNK) family. They are activated by IL-1 and various stress stimuli, playing important roles in gene expression regulation and cell survival.
p38 Mitogen-Activated Protein Kinases (p38 MAPKs)
MAPK10 (JNK3), MAPK11 (p38β), MAPK12 (p38γ), MAPK13 (p38δ), and MAPK14 (p38α): These are members of the p38 MAPK family, which are activated by IL-1 and other stress stimuli. They regulate inflammatory responses, cytokine production, and cellular processes such as proliferation and differentiation.
Other Signaling Molecules
- Mark3: Mark3 is not directly part of IL-1 family signaling but is a protein kinase involved in the regulation of cell morphology and cytoskeletal organization.
- RELA: RELA is a subunit of the NF-κB transcription factor complex. It forms a heterodimer with other NF-κB subunits and translocates into the nucleus upon activation, regulating gene expression.
- TAB1: TAB1 is a regulator of MAP3K7 (TAK1). It enhances the kinase activity of TAK1 in the IL-1 signaling pathway.
- TICAM2 (TRIF): TICAM2, also known as TRIF, is a cytoplasmic adaptor protein involved in Toll-like receptor (TLR) signaling, including TLR3 and TLR4 activation. TRIF mediates the activation of NF-κB and interferon regulatory factor (IRF) pathways.
- TRAF6: TRAF6TRAF6 is a member of the TNF receptor-associated factor (TRAF) family. It plays a critical role in IL-1 family signaling by acting as an adaptor protein. TRAF6 interacts with IL-1 receptor-associated kinases (IRAKs) and facilitates the activation of downstream signaling pathways, including NF-κB and MAPKs. TRAF6 is involved in the regulation of immune and inflammatory responses triggered by IL-1 family cytokines.
In summary, IL-1 family signaling molecules consist of various components that work together to transmit signals from IL-1 receptors and regulate immune responses, inflammation, and cellular processes. These include IκB kinases, transcription factors, inhibitors of NF-κB, IL-1 receptor-associated kinases, MAPK kinases, MAP3K, ERKs, JNKs, p38 MAPKs, and other signaling molecules like TRAF6. Understanding the functions and interactions of these molecules provides insights into the complex mechanisms underlying IL-1 family signaling.
Role of IL-1 Family Signaling Molecules in Disease Development
IL-1 family signaling molecules play crucial roles in immune regulation, inflammatory responses, and the development of various diseases. Here are some key aspects of their involvement:
Immune Regulation
IL-1 family signaling molecules are involved in immune regulation by coordinating immune cell activation, proliferation, and cytokine production. They facilitate communication between immune cells and initiate appropriate immune responses against pathogens or tissue damage.
Inflammatory Response
IL-1 family signaling molecules are potent inducers of inflammation. They promote the production of pro-inflammatory cytokines, such as IL-1β and IL-6, and chemokines, which recruit immune cells to the site of inflammation. This leads to the activation of immune cells, such as macrophages, neutrophils, and T cells, which release additional inflammatory mediators, amplify the response, and help eliminate pathogens or repair damaged tissue.
Autoimmune Diseases
Dysregulation of IL-1 family signaling molecules can contribute to the development of autoimmune diseases, where the immune system mistakenly attacks healthy tissues. For example, elevated levels of IL-1β are implicated in the pathogenesis of diseases like rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel diseases.
Inflammatory Disorders
IL-1 family signaling molecules are associated with various inflammatory disorders, including chronic inflammatory conditions. Excessive or prolonged activation of these signaling pathways can lead to sustained inflammation, tissue damage, and the progression of diseases such as atherosclerosis, chronic obstructive pulmonary disease (COPD), and neuroinflammation in conditions like Alzheimer's disease.
Cancer
IL-1 family signaling molecules have complex roles in cancer development and progression. While they can promote tumor growth and inflammation-associated cancer, they also participate in anti-tumor immune responses. IL-1 signaling can influence tumor cell proliferation, angiogenesis, invasion, and the recruitment and activation of immune cells within the tumor microenvironment.
Therapeutic Target
IL-1 family signaling molecules have emerged as promising therapeutic targets for various inflammatory and autoimmune diseases. Drugs that inhibit IL-1 signaling, such as IL-1 receptor antagonists (IL-1Ra) or antibodies targeting IL-1β, have shown efficacy in treating conditions like rheumatoid arthritis, gout, and autoinflammatory syndromes.
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Related References:
- Boraschi D, Italiani P, Weil S, Martin MU. The family of the interleukin-1 receptors. Immunol Rev. 2018 Jan;281(1):197-232.
- Xu D, Mu R, Wei X. The Roles of IL-1 Family Cytokines in the Pathogenesis of Systemic Sclerosis. Front Immunol. 2019;10:2025. 13.
