Irak requirement for optimal induction by IL-I of multiple signaling pathways

P. Kanakaraji, P. H. Schafer, D. Cavender, K. Ngo, Y. Wul, F. F. Grealish, S. A. Wadsworth, P. A. Peterson, John Siekierka, C. A. Harris, W. P. Fung-Leungl

Research output: Contribution to journalArticle

Abstract

IL 1 is a proinflammatory cytokine with pleiotropic effects in systemic and local inflammatory responses. IL 1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated MAP kinases, c-Jun N-terminal kinase (JNK) and p38, as well as transcription factors such as NFkB. Upon IL-1 binding, IL-1 receptor type 1 forms a complex with IL-1 receptor accessory protein (IL-1R AcP). IL-1 receptor associated kinase (IRAK) rapidly interacts with this receptor complex, becomes phosphorylated and subsequently interacts with other signaling molecules such as TNF receptor associated factor (TRAF6). IRAK is related to Pelle, a Drosophila protein kinase essential for activation of Dorsal, an NF-kB like protein mediated by Toll which is an IL 1 receptor homologue in Drosophila. The association of IRAK with the IL 1 receptor complex, along with its homology to Pelle, suggests that IRAK could play an important role in IL-1 signaling. We generated embryonic fibroblast cells deficient in IRAK to study the role of IRAK in IL-1 mediated signaling and cellular response. The IRAK deficient cells exhibit IL-1 signaling deficiencies which clearly implicate IRAK as an important component of the IL-1 receptor signaling cascade.

Original languageEnglish
JournalFASEB Journal
Volume12
Issue number8
StatePublished - 1 Dec 1998

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Interleukin-1 Receptor-Associated Kinases
interleukin-1
Interleukin-1
Interleukin-1 Receptors
receptors
phosphotransferases (kinases)
Drosophila
Chemical activation
TNF Receptor-Associated Factor 6
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
JNK Mitogen-Activated Protein Kinases
NF-kappa B
Accessories
Fibroblasts
Protein Kinases
mitogen-activated protein kinase
Proteins
Transcription Factors
Phosphotransferases
Cells

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Kanakaraji, P., Schafer, P. H., Cavender, D., Ngo, K., Wul, Y., Grealish, F. F., ... Fung-Leungl, W. P. (1998). Irak requirement for optimal induction by IL-I of multiple signaling pathways. FASEB Journal, 12(8).
Kanakaraji, P. ; Schafer, P. H. ; Cavender, D. ; Ngo, K. ; Wul, Y. ; Grealish, F. F. ; Wadsworth, S. A. ; Peterson, P. A. ; Siekierka, John ; Harris, C. A. ; Fung-Leungl, W. P. / Irak requirement for optimal induction by IL-I of multiple signaling pathways. In: FASEB Journal. 1998 ; Vol. 12, No. 8.
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abstract = "IL 1 is a proinflammatory cytokine with pleiotropic effects in systemic and local inflammatory responses. IL 1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated MAP kinases, c-Jun N-terminal kinase (JNK) and p38, as well as transcription factors such as NFkB. Upon IL-1 binding, IL-1 receptor type 1 forms a complex with IL-1 receptor accessory protein (IL-1R AcP). IL-1 receptor associated kinase (IRAK) rapidly interacts with this receptor complex, becomes phosphorylated and subsequently interacts with other signaling molecules such as TNF receptor associated factor (TRAF6). IRAK is related to Pelle, a Drosophila protein kinase essential for activation of Dorsal, an NF-kB like protein mediated by Toll which is an IL 1 receptor homologue in Drosophila. The association of IRAK with the IL 1 receptor complex, along with its homology to Pelle, suggests that IRAK could play an important role in IL-1 signaling. We generated embryonic fibroblast cells deficient in IRAK to study the role of IRAK in IL-1 mediated signaling and cellular response. The IRAK deficient cells exhibit IL-1 signaling deficiencies which clearly implicate IRAK as an important component of the IL-1 receptor signaling cascade.",
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Kanakaraji, P, Schafer, PH, Cavender, D, Ngo, K, Wul, Y, Grealish, FF, Wadsworth, SA, Peterson, PA, Siekierka, J, Harris, CA & Fung-Leungl, WP 1998, 'Irak requirement for optimal induction by IL-I of multiple signaling pathways', FASEB Journal, vol. 12, no. 8.

Irak requirement for optimal induction by IL-I of multiple signaling pathways. / Kanakaraji, P.; Schafer, P. H.; Cavender, D.; Ngo, K.; Wul, Y.; Grealish, F. F.; Wadsworth, S. A.; Peterson, P. A.; Siekierka, John; Harris, C. A.; Fung-Leungl, W. P.

In: FASEB Journal, Vol. 12, No. 8, 01.12.1998.

Research output: Contribution to journalArticle

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AU - Wadsworth, S. A.

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Kanakaraji P, Schafer PH, Cavender D, Ngo K, Wul Y, Grealish FF et al. Irak requirement for optimal induction by IL-I of multiple signaling pathways. FASEB Journal. 1998 Dec 1;12(8).