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Details on Person Interleukin (IL)-1 family (IL-1?, IL-1? and IL-18) are proin...
| Class:Id | Summation:5607970 |
|---|---|
| _displayName | Interleukin (IL)-1 family (IL-1?, IL-1? and IL-18) are proin... |
| _timestamp | 2014-07-16 02:05:00 |
| created | [InstanceEdit:5607974] Shamovsky, Veronica, 2014-07-14 |
| literatureReference | [LiteratureReference:5607865] IL-1, IL-18, and IL-33 families of cytokines [LiteratureReference:446876] TRAF6 is a signal transducer for interleukin-1 [LiteratureReference:165864] IRAK-4 as the central TIR signaling mediator in innate immunity [LiteratureReference:936987] An oligomeric signaling platform formed by the Toll-like receptor signal transducers MyD88 and IRAK-4 [LiteratureReference:937049] Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling [LiteratureReference:5602396] Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency [LiteratureReference:5602389] Pyogenic bacterial infections in humans with MyD88 deficiency [LiteratureReference:5607909] Infectious diseases in patients with IRAK-4, MyD88, NEMO, or I?B? deficiency [LiteratureReference:5602585] Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity [LiteratureReference:5602701] Primary immunodeficiency to pneumococcal infection due to a defect in Toll-like receptor signaling [LiteratureReference:5262883] IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease [LiteratureReference:5607860] IRAK-4 mutation (Q293X): rapid detection and characterization of defective post-transcriptional TLR/IL-1R responses in human myeloid and non-myeloid cells [LiteratureReference:5602589] Functional assessment of the mutational effects of human IRAK4 and MyD88 genes [LiteratureReference:5607905] MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways [LiteratureReference:446653] Mass spectrometric analysis of the endogenous type I interleukin-1 (IL-1) receptor signaling complex formed after IL-1 binding identifies IL-1RAcP, MyD88, and IRAK-4 as the stable components |
| modified | [InstanceEdit:5609673] Shamovsky, Veronica, 2014-07-16 |
| text | Interleukin (IL)-1 family (IL-1?, IL-1? and IL-18) are proinflammatory cytokines that contribute to host defense in the early steps of the inflammatory response (Arend WP et al. 2008). They bind to the type 1 IL-1 receptor (IL-1R) family members that contain an intracellular domain known as the Toll–IL-1R domain (TIR). Upon ligand binding, IL-1Rs recruits TIR domain-containing adaptor protein, myeloid differentiation primary response protein (MyD88), which in turn binds IRAKs to form Myddosome complex (MyD88:IRAK4:IRAK1/2) leading to the activation of both nuclear factor ?B (NF?B) and mitogen-acivator protein kinases (MAPKs) (Medzhitov R et al. 1998; Cao Z et al. 1996; Suzuki N et al. 2002; Brikos C et al. 2007; Motshwene PG et al. 2009; Lin SC et al. 2010). Studies have identified patients with autosomal recessive (AR) form of IRAK4 deficiency, a health condition with clinical manifestation in infancy or early childhood, that predisposes affected patients to recurrent pyogenic bacterial infection (e.g., Streptococcus pneumoniae and Staphylococcus aureus) (Picard C et al. 2003; Ku CL et al. 2007; Picard C et al. 2010; Picard C et al. 2011). Functional assessment of defective IRAK4 revealed that IL-6 secretion was diminished in monocytes and fibroblasts derived from IRAK4-deficient patients after stimulation with IL-1beta (Picard C. et al. 2003). Other studies confirmed impaired cytokines production by IL-1beta-treated patients cells (Currie AJ et al. 2004; Ku CL et al.2007a,b; Davidson DJ et al. 2010) Interferon-gamma (IFN-?) secretion by patients lymphocytes in response to IL-12 plus IL-1beta or IL-18 was also abolished (Picard C. et al. 2003). SV40-transformed fibroblasts lines from the IRAK4-deficient patients showed impaired activation of both NF?B and p38-MAPK in IL-1R signaling pathway (Picard C. et al. 2003). Here we describe selected mutations, that have been functionally characterized. Cell-based assay as well as in vitro protein-interaction analyses with IRAK4 variants showed that the loss-of-function of defective IRAK4 can be caused by either an abolished protein production as a result of nonsense mutations (e.g.,Q293X and E402X) or an impaired interaction with MyD88 due to missence mutations (e.g., R12C) (Ku CL et al. 2007; Yamamoto T et al. 2014). |
| (summation) | [Pathway:5603038] IRAK4 deficiency (IL1R) [Homo sapiens] |
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No pathways have been reviewed or authored by Interleukin (IL)-1 family (IL-1?, IL-1? and IL-18) are proin... (5607970)
