interleukin-1-mediated signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by interleukin-1 binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:BHF, GOC:mah, GOC:signaling]

Interleukin-1 (IL-1) is a potent pro-inflammatory cytokine that plays a critical role in the immune response to infection and injury. The IL-1 signaling pathway is initiated when IL-1 binds to its receptor, IL-1 receptor (IL-1R). IL-1R is a transmembrane protein that exists as two isoforms, IL-1R1 and IL-1R2. IL-1R1 is the signaling receptor, while IL-1R2 acts as a decoy receptor, preventing IL-1 from binding to IL-1R1. Upon IL-1 binding to IL-1R1, the receptor forms a complex with the adaptor protein MyD88 (Myeloid differentiation primary response 88). MyD88 recruits IRAK4 (IL-1 receptor-associated kinase 4) and IRAK1 (IL-1 receptor-associated kinase 1) to the receptor complex. IRAK4 phosphorylates and activates IRAK1, which in turn activates TRAF6 (TNF receptor-associated factor 6). TRAF6 activates the TAK1 (transforming growth factor-β-activated kinase 1) complex, which consists of TAK1, TAB1 (TAK1-binding protein 1), and TAB2 (TAK1-binding protein 2). The activated TAK1 complex then phosphorylates and activates the MAP kinases (MAPK), including JNK (c-Jun N-terminal kinase), p38 MAPK, and ERK (extracellular signal-regulated kinase). Additionally, TAK1 complex activates the IKK (IκB kinase) complex, which comprises IKKα, IKKβ, and IKKγ (NEMO). The activated IKK complex then phosphorylates IκBα (inhibitor of κBα), leading to its degradation and subsequent nuclear translocation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells). NF-κB is a transcription factor that regulates the expression of numerous pro-inflammatory genes, including those encoding cytokines, chemokines, and adhesion molecules. The IL-1 signaling pathway also activates the transcription factor AP-1 (activator protein 1), which is formed by the dimerization of c-Fos and c-Jun. AP-1 plays a role in the expression of genes involved in cell proliferation, differentiation, and apoptosis. In summary, the IL-1 signaling pathway is a complex cascade of events that ultimately leads to the activation of NF-κB and AP-1, which regulate the expression of genes involved in inflammation, immune response, cell proliferation, and other cellular processes. The dysregulation of this pathway has been implicated in various pathological conditions, including inflammatory diseases, autoimmune disorders, and cancer.'
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Proteins (15)

Compounds (389)