a TKL kinase of the IRAK family. Involved in Toll/IL-1 signaling. One of two putative serine/threonine kinases that become associated with the interleukin-1 receptor following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization. Extensively phosphorylated after its association with IL1-R-1. Polyubiquitinated; after cell stimulation with IL-1-beta. Polyubiquitination occurs with polyubiquitin chains linked through 'Lys-63'. Partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Three isoforms of the human protein and produced by alternative splicing. Isoform 1 binds rapidly but is then degraded allowing isoform 2 to mediate a slower, more sustained response to the cytokine. Isoform 2 is inactive suggesting that the kinase activity of this enzyme is not required for IL-1 signaling. Once phosphorylated, IRAK1 recruits the adapter protein PELI1. Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2. Note: This description may include information from UniProtKB.
Protein type: EC 220.127.116.11; IRAK family; Kinase, protein; Protein kinase, Ser/Thr (non-receptor); Protein kinase, TKL; TKL group
Molecular Function: ATP binding; heat shock protein binding; interleukin-1 receptor binding; kinase activity; nucleotide binding; protein binding; protein heterodimerization activity; protein homodimerization activity; protein kinase activity; protein serine/threonine kinase activity; transferase activity
Biological Process: activation of NF-kappaB-inducing kinase; cellular response to heat; cytokine-mediated signaling pathway; immune system process; innate immune response; JNK cascade; lipopolysaccharide-mediated signaling pathway; negative regulation of cholesterol efflux; negative regulation of NF-kappaB transcription factor activity; negative regulation of transcription, DNA-dependent; phosphorylation; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of interferon type I production; positive regulation of JUN kinase activity; positive regulation of MAP kinase activity; positive regulation of NF-kappaB transcription factor activity; positive regulation of smooth muscle cell proliferation; protein amino acid phosphorylation; protein autophosphorylation; protein oligomerization; regulation of cytokine-mediated signaling pathway; response to lipopolysaccharide; response to peptidoglycan; signal transduction; toll-like receptor 2 signaling pathway; toll-like receptor 4 signaling pathway