Effects of IL-1 receptor-associated kinase (IRAK) expression on IL-1 signaling are independent of its kinase activity.
Interleukin-1 (IL-1) stimulates the association of the IL-1 receptor-associated protein kinase (IRAK) with the heterodimer of IL-IRI and IL-IRAcP via the adapter protein MyD88. In the receptor complex IRAK becomes heavily phosphorylated and concomitantly activated. Here we show that overexpression of a kinase-inactive mutant of IRAK (K239S) inhibits neither IL-1-stimulated activation of the transcription factor NF-kappaB, nor that of the c-Jun N-terminal kinase nor IL-2 production in murine EL-4 cells, but enhances these effects in a manner comparable to wild type IRAK. This strongly suggests that the intrinsic kinase activity is not required for downstream signaling via IRAK.
Knop
J
J
Institut für Molekularpharmakologie, Medizinische Hochschule Hannover, Germany.
Martin
M U
MU
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D053592:Interleukin-1 Receptor-Associated Kinases; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008239:Lysine / Q000235:genetics; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D016296:Mutagenesis; D016328:NF-kappa B / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D012694:Serine / Q000235:genetics; D015398:Signal Transduction; D015533:Transcriptional Activation
D007375:Interleukin-1; D007376:Interleukin-2; D016328:NF-kappa B; D017472:Receptors, Interleukin-1; D012694:Serine; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D008239:Lysine