ArticleMolecular and cellular biology2005
A novel splice variant of interleukin-1 receptor (IL-1R)-associated kinase 1 plays a negative regulatory role in Toll/IL-1R-induced inflammatory signaling.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 102 citations in OpenAlex.
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- RNA processing in innate immunity: regulation by RNA-binding proteins.Trends in biochemical sciences · 2025Review
- Gene Expression of Neurogenesis Related to Exercise Intensity in a Cerebral Infarction Rat Model.International journal of molecular sciences · 2024Article
- RNA Binding Proteins that Mediate LPS-induced Alternative Splicing of the MyD88 Innate Immune Regulator.Journal of molecular biology · 2024Article
- BLK positively regulates TLR/IL-1R signaling by catalyzing TOLLIP phosphorylation.The Journal of cell biology · 2024Article
- Adaptor molecules mediate negative regulation of macrophage inflammatory pathways: a closer look.Frontiers in immunology · 2024Review
- Interleukin Receptor Associated Kinase 1 Signaling and Its Association with Cardiovascular Diseases.Reviews in cardiovascular medicine · 2022Review
- Alternative pre-mRNA splicing as a mechanism for terminating Toll-like Receptor signaling.Frontiers in immunology · 2022Review
- The three as: Alternative splicing, alternative polyadenylation and their impact on apoptosis in immune function.Immunological reviews · 2021Review
- Inhibitory feedback control of NF-κB signalling in health and disease.The Biochemical journal · 2021Review
- Shaping the Innate Immune Response Through Post-Transcriptional Regulation of Gene Expression Mediated by RNA-Binding Proteins.Frontiers in immunology · 2021Review
- Discovery of a Selective, Covalent IRAK1 Inhibitor with Antiproliferative Activity in MYD88 Mutated B-Cell Lymphoma.ACS medicinal chemistry letters · 2020Article
- Interleukin-1 Receptor-Associated Kinase (IRAK) Signaling in Kaposi Sarcoma-Associated Herpesvirus-Induced Primary Effusion Lymphoma.Journal of virology · 2020Article
- NF-κB mediates lipopolysaccharide-induced alternative pre-mRNA splicing ofThe Journal of biological chemistry · 2020Article
- X-Linked IRAK1 Polymorphism is Associated with Sex-Related Differences in Polymorphonuclear Granulocyte and Monocyte Activation and Response Variabilities.Shock (Augusta, Ga.) · 2020Article
- Inflammation-Induced Alternative Pre-mRNA Splicing in Mouse Alveolar Macrophages.G3 (Bethesda, Md.) · 2020Article
- Directional X Chromosome Skewing of White Blood Cells from Subjects with Heterozygous Mosaicism for the Variant IRAK1 Haplotype.Inflammation · 2020Article
- The Splicing Factor hnRNP M Is a Critical Regulator of Innate Immune Gene Expression in Macrophages.Cell reports · 2019Article
- Interleukin-1 Receptor Associated Kinase 1 Mediates the Maintenance of Neuropathic Pain after Chronic Constriction Injury in Rats.Neurochemical research · 2019Article
- RNA Splicing: A New Paradigm in Host-Pathogen Interactions.Journal of molecular biology · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interleukin-1 (IL-1) receptor-associated kinase 1 (IRAK1) is a member of the IRAK kinase family that plays a pivotal role in the Toll/IL-1 receptor (TIR) family signaling cascade. We have identified a novel splice variant, IRAK1c, which lacks a region encoded by exon 11 of the IRAK1 gene. IRAK1c expression was confirmed by both RNA and protein detection. Although both IRAK1 and IRAK1c are expressed in most tissues tested, IRAK1c is the predominant form of IRAK1 expressed in the brain. Unlike IRAK1, IRAK1c lacks kinase activity and cannot be phosphorylated by IRAK4. However, IRAK1c retains the ability to strongly interact with IRAK2, MyD88, Tollip, and TRAF6. Overexpression of IRAK1c suppressed NF-kappaB activation and blocked IL-1beta-induced IL-6 as well as lipopolysaccharide- and CpG-induced tumor necrosis factor alpha production in multiple cellular systems. Mechanistically, we provide evidence that IRAK1c functions as a dominant negative by failing to be phosphorylated by IRAK4, thus remaining associated with Tollip and blocking NF-kappaB activation. The presence of a regulated, alternative splice variant of IRAK1 that functions as a kinase-dead, dominant-negative protein adds further complexity to the variety of mechanisms that regulate TIR signaling and the subsequent inflammatory response.
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