Modulation of tumor necrosis factor and interleukin-1-dependent NF-κB activity by mPLK/IRAK

Eva Vig, Melissa Green, Yuanwen Liu, David B. Donner, Naofumi Mukaida, Mark Goebl, Maureen Harrington

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

The innate immune response is an important defense against pathogenic agents. A component of this response is the NF-κB-dependent activation of genes encoding inflammatory cytokines such as interleukin-8 (IL-8) and cell adhesion molecules like E-selectin. Members of the serine/threonine innate immune kinase family of proteins have been proposed to mediate the innate immune response. One serine/threonine innate immune kinase family member, the mouse Pelle-like kinase/human interleukin-1 receptor-associated kinase (mPLK/IRAK), has been proposed to play an obligate role in promoting IL-1- mediated inflammation. However, it is currently unknown whether mPLK/IRAK catalytic activity is required for IL-1-dependent NF-κB activation. The present study demonstrates that mPLK/IRAK catalytic activity is not required for IL-1-mediated activation of an NF-κB-dependent signal. Intriguingly, catalytically inactive mPLK/IRAK inhibits type 1 tumor necrosis factor (TNF) receptor-dependent NF-κB activation. The pathway through which mPLK/IRAK mediates this TNF response is TRADD- and TRAF2-independent. Our data suggest that in addition to its role in IL-1 signaling, mPLK/IRAK is a component of a novel signal transduction pathway through which TNF R1 activates NF-κB- dependent gene expression.

Original languageEnglish
Pages (from-to)13077-13084
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number19
DOIs
StatePublished - May 7 1999

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Interleukin-1 Receptor-Associated Kinases
Interleukin-1
Phosphotransferases
Tumor Necrosis Factor-alpha
Modulation
Chemical activation
Threonine
Innate Immunity
Serine
TNF Receptor-Associated Factor 2
Catalyst activity
Receptors, Tumor Necrosis Factor, Type I
E-Selectin
Tumor Necrosis Factor Receptors
Signal transduction
Cell Adhesion Molecules
Gene encoding
Interleukin-8
Protein Kinases
Transcriptional Activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Modulation of tumor necrosis factor and interleukin-1-dependent NF-κB activity by mPLK/IRAK. / Vig, Eva; Green, Melissa; Liu, Yuanwen; Donner, David B.; Mukaida, Naofumi; Goebl, Mark; Harrington, Maureen.

In: Journal of Biological Chemistry, Vol. 274, No. 19, 07.05.1999, p. 13077-13084.

Research output: Contribution to journalArticle

Vig, Eva ; Green, Melissa ; Liu, Yuanwen ; Donner, David B. ; Mukaida, Naofumi ; Goebl, Mark ; Harrington, Maureen. / Modulation of tumor necrosis factor and interleukin-1-dependent NF-κB activity by mPLK/IRAK. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 19. pp. 13077-13084.
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