IRAK3
Interleukin-1 receptor-associated kinase 3 (originally IRAK-M) is an enzyme that in humans is encoded by the IRAK3 gene. The IRAK family of proteins consists of two active serine/threonine kinases IRAK-1 and IRAK-4, as well as two inactive kinases IRAK-2 and IRAK-3. The activity of IRAK-3 is induced by toll-like receptor and interleukin-1 receptor signaling. IRAK-3 acts as a negative regulator for downstream signaling through these pathways by preventing the phosphorylation of IRAK-1 and IRAK-4 or by inhibiting their dissociation from the Mydd88 complex. Using in vivo liposome-mediated delivery of CRISPR/Cas9 plasmid expressing IRAK3 gRNA, IRAK3 was shown to be responsible for endotoxin-induced expression of A20 and VE-cadherin in endothelial cells. Thus, IRAK3 is crucial for maintenance and repair of endothelial barrier after endotoxin-induced lung injury.
References
- 1 2 3 GRCh38: Ensembl release 89: ENSG00000090376 – Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020227 – Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ Wesche H, Gao X, Li X, Kirschning CJ, Stark GR, Cao Z (July 1999). "IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family". The Journal of Biological Chemistry. 274 (27): 19403–10. doi:10.1074/jbc.274.27.19403. PMID 10383454.
- ↑ "Entrez Gene: IRAK3 interleukin-1 receptor-associated kinase 3".
- ↑ Kobayashi K, Hernandez LD, Galán JE, Janeway CA Jr, Medzhitov R, Flavell RA (July 2002). "IRAK-M is a negative regulator of Toll-like receptor signaling". Cell. 110 (2): 191–202. doi:10.1016/s0092-8674(02)00827-9. PMID 12150927.
- ↑ Soni D, Wang DM, Regmi SC, Mittal M, Vogel SM, Schlüter D, Tiruppathi C (May 2018). "Deubiquitinase function of A20 maintains and repairs endothelial barrier after lung vascular injury". Cell Death Discovery. 4 (60) 60. doi:10.1038/s41420-018-0056-3. PMC 5955943. PMID 29796309.
Further reading
- Rosati O, Martin MU (May 2002). "Identification and characterization of murine IRAK-M". Biochemical and Biophysical Research Communications. 293 (5): 1472–7. Bibcode:2002BBRC..293.1472R. doi:10.1016/S0006-291X(02)00411-4. PMID 12054681.
- Bin LH, Xu LG, Shu HB (July 2003). "TIRP, a novel Toll/interleukin-1 receptor (TIR) domain-containing adapter protein involved in TIR signaling". The Journal of Biological Chemistry. 278 (27): 24526–32. doi:10.1074/jbc.M303451200. PMID 12721283.
- Escoll P, del Fresno C, García L, Vallés G, Lendínez MJ, Arnalich F, López-Collazo E (November 2003). "Rapid up-regulation of IRAK-M expression following a second endotoxin challenge in human monocytes and in monocytes isolated from septic patients". Biochemical and Biophysical Research Communications. 311 (2): 465–72. Bibcode:2003BBRC..311..465E. doi:10.1016/j.bbrc.2003.10.019. PMID 14592437.
- del Fresno C, Otero K, Gómez-García L, González-León MC, Soler-Ranger L, Fuentes-Prior P, Escoll P, Baos R, Caveda L, García F, Arnalich F, López-Collazo E (March 2005). "Tumor cells deactivate human monocytes by up-regulating IL-1 receptor associated kinase-M expression via CD44 and TLR4". Journal of Immunology. 174 (5): 3032–40. doi:10.4049/jimmunol.174.5.3032. PMID 15728517.
- Su J, Xie Q, Wilson I, Li L (July 2007). "Differential regulation and role of interleukin-1 receptor associated kinase-M in innate immunity signaling". Cellular Signalling. 19 (7): 1596–601. doi:10.1016/j.cellsig.2007.02.009. PMC 1978187. PMID 17379480.
- Balaci L, Spada MC, Olla N, Sole G, Loddo L, Anedda F, Naitza S, Zuncheddu MA, Maschio A, Altea D, Uda M, Pilia S, Sanna S, Masala M, Crisponi L, Fattori M, Devoto M, Doratiotto S, Rassu S, Mereu S, Giua E, Cadeddu NG, Atzeni R, Pelosi U, Corrias A, Perra R, Torrazza PL, Pirina P, Ginesu F, Marcias S, Schintu MG, Del Giacco GS, Manconi PE, Malerba G, Bisognin A, Trabetti E, Boner A, Pescollderungg L, Pignatti PF, Schlessinger D, Cao A, Pilia G (June 2007). "IRAK-M is involved in the pathogenesis of early-onset persistent asthma". American Journal of Human Genetics. 80 (6): 1103–14. doi:10.1086/518259. PMC 1867098. PMID 17503328.
- Weersma RK, Oostenbrug LE, Nolte IM, Van Der Steege G, Oosterom E, Van Dullemen HM, Kleibeuker JH, Dijkstra G (July 2007). "Association of interleukin-1 receptor-associated kinase M (IRAK-M) and inflammatory bowel diseases". Scandinavian Journal of Gastroenterology. 42 (7): 827–33. doi:10.1080/00365520601114024. PMID 17558906. S2CID 22703718.
- van 't Veer C, van den Pangaart PS, van Zoelen MA, de Kruif M, Birjmohun RS, Stroes ES, de Vos AF, van der Poll T (November 2007). "Induction of IRAK-M is associated with lipopolysaccharide tolerance in a human endotoxemia model". Journal of Immunology. 179 (10): 7110–20. doi:10.4049/jimmunol.179.10.7110. PMID 17982103.
External links
- Overview of all the structural information available in the PDB for UniProt: Q9Y616 (Interleukin-1 receptor-associated kinase 3) at the PDBe-KB.
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