Overexpression of an enzymically inactive interleukin-1-receptor-associated kinase activates nuclear factor-kappaB.
Upon interleukin 1 (IL-1) stimulation, the IL-1-receptor (IL-1R)-associated kinase (IRAK) is rapidly recruited to the IL-1R complex and undergoes phosphorylation. Here we demonstrate that recombinant wild-type IRAK (IRAK-WT), but not a kinase-defective mutant with Asp340 replaced by an asparagine residue (IRAK-Asp340Asn), is highly phosphorylated and is capable of auto-phosphorylation in vitro. Overexpression of both IRAK-WT and IRAK-Asp340Asn caused activation of nuclear factor kappaB, suggesting that the kinase activity of IRAK is not required outside of the IL-1R complex.
Maschera
B
B
Glaxo Wellcome, Cell Biology Unit, Gunnels Wood Road, Stevenage SG1 2NY, UK. bm45459@GlaxoWellcome.co.uk
Ray
K
K
Burns
K
K
Volpe
F
F
D000595:Amino Acid Sequence; D000818:Animals; D001216:Asparagine / Q000737:chemistry / Q000378:metabolism; D001224:Aspartic Acid / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D018411:Spodoptera; D014158:Transcription, Genetic
D017931:DNA Primers; D018076:DNA, Complementary; D016328:NF-kappa B; D001224:Aspartic Acid; D001216:Asparagine; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases