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Science 23 February 1996:
Vol. 271. no. 5252, pp. 1128 - 1131
DOI: 10.1126/science.271.5252.1128
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Reports

IRAK: A Kinase Associated with the Interleukin-1 Receptor

Zhaodan Cao, (1) William J. Henzel, Xiong Gao

The pleiotropic biological activities of interleukin-1 (IL-1) are mediated by its type I receptor (IL-1RI). When the ligand binds, IL-1RI initiates a signaling cascade that results in the activation of the transcription regulator nuclear factor kappa B (NF-kappa B). A protein kinase designated IRAK (IL-1 receptor-associated kinase) was purified, and its complementary DNA was molecularly cloned. When human embryonic kidney cells (cell line 293) overexpressing IL-1RI or HeLa cells were exposed to IL-1, IRAK rapidly associated with the IL-1RI complex and was phosphorylated. The primary amino acid sequence of IRAK shares similarity with that of Pelle, a protein kinase that is essential for the activation of a NF-kappa B homolog in Drosophila.

Z. Cao and X. Gao, Molecular Biology Department, Tularik, Incorporated, South San Francisco, CA 94080, USA.
W. J. Henzel, Protein Chemistry Department, Genentech, Incorporated, South San Francisco, CA 94080, USA.
(1) To whom correspondence should be addressed. E-mail: cao{at}tularik.com


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Molecular Description of Evolving Paclitaxel Resistance in the SKOV-3 Human Ovarian Carcinoma Cell Line.
D. E. Lamendola, Z. Duan, R. Z. Yusuf, and M. V. Seiden (2003)
Cancer Res. 63, 2200-2205
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Role of the MyD88 transduction signaling pathway in endothelial activation by antiphospholipid antibodies.
E. Raschi, C. Testoni, D. Bosisio, M. O. Borghi, T. Koike, A. Mantovani, and P. L. Meroni (2003)
Blood 101, 3495-3500
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Regulation of the Interleukin-1-induced Signaling Pathways by a Novel Member of the Protein Phosphatase 2C Family (PP2Cepsilon ).
M. G. Li, K. Katsura, H. Nomiyama, K.-i. Komaki, J. Ninomiya-Tsuji, K. Matsumoto, T. Kobayashi, and S. Tamura (2003)
J. Biol. Chem. 278, 12013-12021
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Identification of TIFA as an Adapter Protein That Links Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) to Interleukin-1 (IL-1) Receptor-associated Kinase-1 (IRAK-1) in IL-1 Receptor Signaling.
H. Takatsuna, H. Kato, J. Gohda, T. Akiyama, A. Moriya, Y. Okamoto, Y. Yamagata, M. Otsuka, K. Umezawa, K. Semba, et al. (2003)
J. Biol. Chem. 278, 12144-12150
   Abstract »    Full Text »    PDF »
Pyogenic Bacterial Infections in Humans with IRAK-4 Deficiency.
C. Picard, A. Puel, M. Bonnet, C.-L. Ku, J. Bustamante, K. Yang, C. Soudais, S. Dupuis, J. Feinberg, C. Fieschi, et al. (2003)
Science 299, 2076-2079
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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.
Z. Jiang, H. J. Johnson, H. Nie, J. Qin, T. A. Bird, and X. Li (2003)
J. Biol. Chem. 278, 10952-10956
   Abstract »    Full Text »    PDF »
Pelle kinase is activated by autophosphorylation during Toll signaling in Drosophila.
B. Shen and J. L. Manley (2003)
Development 129, 1925-1933
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TAB2 Is Essential for Prevention of Apoptosis in Fetal Liver but Not for Interleukin-1 Signaling.
H. Sanjo, K. Takeda, T. Tsujimura, J. Ninomiya-Tsuji, K. Matsumoto, and S. Akira (2003)
Mol. Cell. Biol. 23, 1231-1238
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Mal and MyD88: adapter proteins involved in signal transduction by Toll-like receptors.
L. A.J. O'Neill, A. Dunne, M. Edjeback, P. Gray, C. Jefferies, and C. Wietek (2003)
Innate Immunity 9, 55-59
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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.
K. Burns, S. Janssens, B. Brissoni, N. Olivos, R. Beyaert, and J. Tschopp (2003)
J. Exp. Med. 197, 263-268
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Molecular Mechanisms for Lipopolysaccharide-induced Biphasic Activation of Nuclear Factor-kappa B (NF-kappa B).
S.-J. Han, H.-M. Ko, J.-H. Choi, K. H. Seo, H.-S. Lee, E.-K. Choi, I.-W. Choi, H.-K. Lee, and S.-Y. Im (2002)
J. Biol. Chem. 277, 44715-44721
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Interleukin-1 (IL-1) Receptor-Associated Kinase-Dependent IL-1-Induced Signaling Complexes Phosphorylate TAK1 and TAB2 at the Plasma Membrane and Activate TAK1 in the Cytosol.
Z. Jiang, J. Ninomiya-Tsuji, Y. Qian, K. Matsumoto, and X. Li (2002)
Mol. Cell. Biol. 22, 7158-7167
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Cutting Edge: Mouse Pellino-2 Modulates IL-1 and Lipopolysaccharide Signaling.
K.-Y. Yu, H.-J. Kwon, D. A. M. Norman, E. Vig, M. G. Goebl, and M. A. Harrington (2002)
J. Immunol. 169, 4075-4078
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IL-1{beta} potentiates heat-activated currents in rat sensory neurons: involvement of IL-1RI, tyrosine kinase, and protein kinase C.
O. OBREJA, P. K. RATHEE, K. S. LIPS, C. DISTLER, and M. KRESS (2002)
FASEB J 16, 1497-1503
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A heterotrimeric death domain complex in Toll signaling.
H. Sun, B. N. Bristow, G. Qu, and S. A. Wasserman (2002)
PNAS 99, 12871-12876
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Identification of Threonine 66 as a Functionally Critical Residue of the Interleukin-1 Receptor-associated Kinase.
K. Ross, L. Yang, S. Dower, F. Volpe, and F. Guesdon (2002)
J. Biol. Chem. 277, 37414-37421
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Signal Transduction Pathways Involved in Rheumatoid Arthritis Synovial Fibroblast Interleukin-18-induced Vascular Cell Adhesion Molecule-1 Expression.
J. C. M. Morel, C. C. Park, K. Zhu, P. Kumar, J. H. Ruth, and A. E. Koch (2002)
J. Biol. Chem. 277, 34679-34691
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Narrowing in on the causative defect of an intriguing X-linked myopathy with excessive autophagy.
B. A. Minassian, R. Aiyar, S. Alic, B. Banwell, M. Villanova, M. Fardeau, J. W. Mandell, V. C. Juel, M. Rafii, M. Auranen, et al. (2002)
Neurology 59, 596-601
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IRAK contributes to burn-triggered myocardial contractile dysfunction.
J. A. Thomas, M. F. Tsen, D. J. White, and J. W. Horton (2002)
Am J Physiol Heart Circ Physiol 283, H829-H836
   Abstract »    Full Text »    PDF »


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