Interleukin 1 Receptor Associated Kinase 1 (IRAK1)

IRAK1; IRAK; Pelle

SPN	V320
HGNC	6112
MGI	107420
PubMed	23845443
RGD	1563841
UniProt	P51617
Wiki	IRAK1

Interleukin-1 receptor-associated kinase 1 is one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.Cao et al. (1996) purified an IL1R-associated kinase, IRAK, and cloned its cDNA from human embryonic kidney cells. The deduced 712-amino acid protein has a calculated molecular mass of about 76 kD. IRAK shares significant similarity with Pelle, a protein kinase essential for activation of an NF-kappa-B homolog in Drosophila. Northern blot analysis detected a 3.5-kb transcript in all human tissues examined.

Reference

"IRAK: a kinase associated with the interleukin-1 receptor."
Science 271:1128-1131(1996) [PubMed] [Europe PMC] [Abstract]

"Comparative sequence analysis of the MECP2-locus in human and mouse reveals new transcribed regions."
Mamm. Genome 11:182-190(2000) [PubMed] [Europe PMC] [Abstract]

"IRAK1b, a novel alternative splice variant of interleukin-1 receptor-associated kinase (IRAK), mediates interleukin-1 signaling and has prolonged stability."
J. Biol. Chem. 276:29037-29044(2001) [PubMed] [Europe PMC] [Abstract]

"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."
Mol. Cell. Biol. 25:6521-6532(2005) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence of the human X chromosome."
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"MyD88: an adapter that recruits IRAK to the IL-1 receptor complex."
Immunity 7:837-847(1997) [PubMed] [Europe PMC] [Abstract]

"Tollip, a new component of the IL-1R1 pathway, links IRAK to the IL-1 receptor."
Nat. Cell Biol. 2:346-351(2000) [PubMed] [Europe PMC] [Abstract]

"IRAK4: a novel member of the IRAK family with the properties of an IRAK-kinase."
Proc. Natl. Acad. Sci. U.S.A. 99:5567-5572(2002) [PubMed] [Europe PMC] [Abstract]

"Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex."
J. Biol. Chem. 278:10952-10956(2003) [PubMed] [Europe PMC] [Abstract]

"Characterization of Pellino2, a substrate of IRAK1 and IRAK4."
FEBS Lett. 547:157-161(2003) [PubMed] [Europe PMC] [Abstract]

"Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4."
J. Exp. Med. 197:263-268(2003) [PubMed] [Europe PMC] [Abstract]

"Pellino3, a novel member of the Pellino protein family, promotes activation of c-Jun and Elk-1 and may act as a scaffolding protein."
J. Immunol. 171:1500-1506(2003) [PubMed] [Europe PMC] [Abstract]

"Regulation of interleukin receptor-associated kinase (IRAK) phosphorylation and signaling by iota protein kinase C."
J. Biol. Chem. 279:4161-4165(2004) [PubMed] [Europe PMC] [Abstract]

"Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling."
J. Biol. Chem. 279:5227-5236(2004) [PubMed] [Europe PMC] [Abstract]

"IRAK4 kinase activity is redundant for interleukin-1 (IL-1) receptor-associated kinase phosphorylation and IL-1 responsiveness."
J. Biol. Chem. 279:26748-26753(2004) [PubMed] [Europe PMC] [Abstract]

"IRAK1 serves as a novel regulator essential for lipopolysaccharide-induced interleukin-10 gene expression."
J. Biol. Chem. 279:51697-51703(2004) [PubMed] [Europe PMC] [Abstract]

"IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST 2 and induces T helper type 2-associated cytokines."
Immunity 23:479-490(2005) [PubMed] [Europe PMC] [Abstract]

"Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction."
J. Exp. Med. 201:915-923(2005) [PubMed] [Europe PMC] [Abstract]

"Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1."
Nat. Immunol. 7:1057-1065(2006) [PubMed] [Europe PMC] [Abstract]

"Differential regulation of interleukin-1 receptor associated kinase 1 (IRAK1) splice variants."
Mol. Immunol. 44:900-905(2007) [PubMed] [Europe PMC] [Abstract]

"The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1."
Biochem. J. 409:43-52(2008) [PubMed] [Europe PMC] [Abstract]

"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]

"Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation."
Mol. Cell. Biol. 28:3538-3547(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Direct activation of protein kinases by unanchored polyubiquitin chains."
Nature 461:114-119(2009) [PubMed] [Europe PMC] [Abstract]

"IRAK1 and IRAK4 promote phosphorylation, ubiquitination, and degradation of MyD88 adaptor-like (Mal)."
J. Biol. Chem. 285:18276-18282(2010) [PubMed] [Europe PMC] [Abstract]

"IRAK1: a critical signaling mediator of innate immunity."
Cell. Signal. 20:269-276(2008) [PubMed] [Europe PMC] [Abstract]

"The Pellino family: IRAK E3 ligases with emerging roles in innate immune signalling."
Trends Immunol. 30:33-42(2009) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Patterns of somatic mutation in human cancer genomes."
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]