Overexpression of an enzymically inactive interleukin-1-receptor-associated kinase activates nuclear factor-κB

被引：79

作者：

Maschera, B

Ray, K

Burns, K

Volpe, F

机构：

[1] Glaxo Wellcome, Cell Biol Unit, Stevenage SG1 2NY, Herts, England

[2] Univ Lausanne, Inst Biochem, CH-10066 Epalinges, Switzerland

来源：

BIOCHEMICAL JOURNAL | 1999年 / 339卷

关键词：

IL-1; signalling; IRAK-2; NF-kappa B-inducing kinase (NIK);

D O I：

10.1042/0264-6021:3390227

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Upon interleukin 1 (IL-1) stimulation, the IL-1-receptor (IL-IR)associated kinase (IRAK) is rapidly recruited to the IL-IR complex and undergoes phosphorylation. Here we demonstrate that recombinant wild-type IRAK (IRAK-WT), but not a kinase-defective mutant with Asp(340) replaced by an asparagine residue (IRAK-Asp(390)Asn), is highly phosphorylated and is capable of auto-phosphorylation in vitro. Overexpression of both IRAK-WT and IRAK-sp(340)Asn caused activation of nuclear factor kappa B, suggesting that the kinase activity of IRAK is not required outside of the IL-IR complex.

引用

收藏

页码：227 / 231

页数：5

相关论文

共 25 条

[11] Recruitment of IRAK to the interleukin 1 receptor complex requires interleukin 1 receptor accessory protein [J].

Huang, JN ;

Gao, X ;

Li, S ;

Cao, ZD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (24) :12829-12832

[12] Interleukin (IL)-1 receptor-associated kinase (IRAK) requirement for optimal induction of multiple IL-1 signaling pathways and IL-6 production [J].

Kanakaraj, P ;

Schafer, PH ;

Cavender, DE ;

Wu, Y ;

Ngo, K ;

Grealish, PF ;

Wadsworth, SA ;

Peterson, PA ;

Siekierka, JJ ;

Harris, CA ;

Fung-Leung, WP .

JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (12) :2073-2079

[13] MAP3K-related kinase involved in NF-kappa B induction by TNF, CD95 and IL-1 [J].

Malinin, NL ;

Boldin, MP ;

Kovalenko, AV ;

Wallach, D .

NATURE, 1997, 385 (6616) :540-544

[14]

Martin MU, 1997, EUR CYTOKINE NETW, V8, P5

[15] RIP2 is a novel NF-κB-activating and cell death-inducing kinase [J].

McCarthy, JV ;

Ni, J ;

Dixit, VM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (27) :16968-16975

[16] IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling [J].

Muzio, M ;

Ni, J ;

Feng, P ;

Dixit, VM .

SCIENCE, 1997, 278 (5343) :1612-1615

[17] Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants [J].

O'Neill, LAJ ;

Greene, C .

JOURNAL OF LEUKOCYTE BIOLOGY, 1998, 63 (06) :650-657

[18]

Ray KP, 1997, BIOCHEM J, V328, P707

[19] Biochemical characterization of the protein tyrosine kinase homology domain of the ErbBB (HER3) receptor protein [J].

Sierke, SL ;

Cheng, KR ;

Kim, HH ;

Koland, JG .

BIOCHEMICAL JOURNAL, 1997, 322 :757-763

[20] Cytosolic domain of the type I interleukin-1 receptor spontaneously recruits signaling molecules to activate a proinflammatory gene [J].

Singh, R ;

Huang, S ;

Guth, T ;

Konieczkowski, M ;

Sedor, JR .

JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (02) :419-428