Functional role of c-Src in IL-1-induced NF-κB activation: c-Src is a component of the IKK complex

Megumi Tago, Kenji Tago, Kumi Andoh, Yoshiko Sonoda, Shin Ichi Tominaga, Tadashi Kasahara

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Interleukin-1 (IL-1) mediates numerous host responses through the rapid activation of nuclear factor-κB (NF-κB), but the signal pathways leading to NF-κB activation are regulated at multiple stages. Here, we propose a novel regulatory system for IL-1-induced NF-κB activation by a tyrosine kinase, c-Src. The kinase activity of c-Src increases in an IL-1-dependent manner and the ectopic expression of c-Src augments IL-1-induced NF-κB activation, suggesting the involvement of c-Src in IL-1 signaling. However, a Src family inhibitor, PP2 failed to inhibit IL-1-induced NF-κB activation, and the expression of a c-Src mutant lacking kinase activity (c-Src KD) augmented IL-1-induced NF-κB activation as well as wild type c-Src, indicating that the tyrosine kinase activity is not required for IL-1-induced NF-κB activation. Furthermore, a physiological interaction between c-Src and Iκc;B kinase γ (IKKγ) was observed, implying the involvement of c-Src in the IKK-complex. While c-Src augmented IL-1-induced IKK activation independent of its kinase activity, the region comprising amino acids 361-440 in the c-Src kinase domain are required for NF-κB; activation. The same region of c-Src is also required for IL-1-induced IKK activation and the association with IKKγ. Taken together, our results suggest that c-Src plays a critical role in IL-1-induced NF-κB activation through the IKK complex.

Original languageEnglish
Pages (from-to)189-197
Number of pages9
JournalJournal of Biochemistry
Volume137
Issue number2
DOIs
Publication statusPublished - 2005 Feb

Fingerprint

Interleukin-1
Chemical activation
Phosphotransferases
Protein-Tyrosine Kinases
Signal Transduction
CSK tyrosine-protein kinase
Association reactions
Amino Acids

Keywords

  • c-Src
  • c-Src KD
  • IκB-Complex
  • IKKγ
  • IL-1-induced NF-κB activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Functional role of c-Src in IL-1-induced NF-κB activation : c-Src is a component of the IKK complex. / Tago, Megumi; Tago, Kenji; Andoh, Kumi; Sonoda, Yoshiko; Tominaga, Shin Ichi; Kasahara, Tadashi.

In: Journal of Biochemistry, Vol. 137, No. 2, 02.2005, p. 189-197.

Research output: Contribution to journalArticle

Tago, Megumi ; Tago, Kenji ; Andoh, Kumi ; Sonoda, Yoshiko ; Tominaga, Shin Ichi ; Kasahara, Tadashi. / Functional role of c-Src in IL-1-induced NF-κB activation : c-Src is a component of the IKK complex. In: Journal of Biochemistry. 2005 ; Vol. 137, No. 2. pp. 189-197.
@article{5f6de4a3af914588876ade925478824c,
title = "Functional role of c-Src in IL-1-induced NF-κB activation: c-Src is a component of the IKK complex",
abstract = "Interleukin-1 (IL-1) mediates numerous host responses through the rapid activation of nuclear factor-κB (NF-κB), but the signal pathways leading to NF-κB activation are regulated at multiple stages. Here, we propose a novel regulatory system for IL-1-induced NF-κB activation by a tyrosine kinase, c-Src. The kinase activity of c-Src increases in an IL-1-dependent manner and the ectopic expression of c-Src augments IL-1-induced NF-κB activation, suggesting the involvement of c-Src in IL-1 signaling. However, a Src family inhibitor, PP2 failed to inhibit IL-1-induced NF-κB activation, and the expression of a c-Src mutant lacking kinase activity (c-Src KD) augmented IL-1-induced NF-κB activation as well as wild type c-Src, indicating that the tyrosine kinase activity is not required for IL-1-induced NF-κB activation. Furthermore, a physiological interaction between c-Src and Iκc;B kinase γ (IKKγ) was observed, implying the involvement of c-Src in the IKK-complex. While c-Src augmented IL-1-induced IKK activation independent of its kinase activity, the region comprising amino acids 361-440 in the c-Src kinase domain are required for NF-κB; activation. The same region of c-Src is also required for IL-1-induced IKK activation and the association with IKKγ. Taken together, our results suggest that c-Src plays a critical role in IL-1-induced NF-κB activation through the IKK complex.",
keywords = "c-Src, c-Src KD, IκB-Complex, IKKγ, IL-1-induced NF-κB activation",
author = "Megumi Tago and Kenji Tago and Kumi Andoh and Yoshiko Sonoda and Tominaga, {Shin Ichi} and Tadashi Kasahara",
year = "2005",
month = "2",
doi = "10.1093/jb/mvi018",
language = "English",
volume = "137",
pages = "189--197",
journal = "Journal of Biochemistry",
issn = "0021-924X",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Functional role of c-Src in IL-1-induced NF-κB activation

T2 - c-Src is a component of the IKK complex

AU - Tago, Megumi

AU - Tago, Kenji

AU - Andoh, Kumi

AU - Sonoda, Yoshiko

AU - Tominaga, Shin Ichi

AU - Kasahara, Tadashi

PY - 2005/2

Y1 - 2005/2

N2 - Interleukin-1 (IL-1) mediates numerous host responses through the rapid activation of nuclear factor-κB (NF-κB), but the signal pathways leading to NF-κB activation are regulated at multiple stages. Here, we propose a novel regulatory system for IL-1-induced NF-κB activation by a tyrosine kinase, c-Src. The kinase activity of c-Src increases in an IL-1-dependent manner and the ectopic expression of c-Src augments IL-1-induced NF-κB activation, suggesting the involvement of c-Src in IL-1 signaling. However, a Src family inhibitor, PP2 failed to inhibit IL-1-induced NF-κB activation, and the expression of a c-Src mutant lacking kinase activity (c-Src KD) augmented IL-1-induced NF-κB activation as well as wild type c-Src, indicating that the tyrosine kinase activity is not required for IL-1-induced NF-κB activation. Furthermore, a physiological interaction between c-Src and Iκc;B kinase γ (IKKγ) was observed, implying the involvement of c-Src in the IKK-complex. While c-Src augmented IL-1-induced IKK activation independent of its kinase activity, the region comprising amino acids 361-440 in the c-Src kinase domain are required for NF-κB; activation. The same region of c-Src is also required for IL-1-induced IKK activation and the association with IKKγ. Taken together, our results suggest that c-Src plays a critical role in IL-1-induced NF-κB activation through the IKK complex.

AB - Interleukin-1 (IL-1) mediates numerous host responses through the rapid activation of nuclear factor-κB (NF-κB), but the signal pathways leading to NF-κB activation are regulated at multiple stages. Here, we propose a novel regulatory system for IL-1-induced NF-κB activation by a tyrosine kinase, c-Src. The kinase activity of c-Src increases in an IL-1-dependent manner and the ectopic expression of c-Src augments IL-1-induced NF-κB activation, suggesting the involvement of c-Src in IL-1 signaling. However, a Src family inhibitor, PP2 failed to inhibit IL-1-induced NF-κB activation, and the expression of a c-Src mutant lacking kinase activity (c-Src KD) augmented IL-1-induced NF-κB activation as well as wild type c-Src, indicating that the tyrosine kinase activity is not required for IL-1-induced NF-κB activation. Furthermore, a physiological interaction between c-Src and Iκc;B kinase γ (IKKγ) was observed, implying the involvement of c-Src in the IKK-complex. While c-Src augmented IL-1-induced IKK activation independent of its kinase activity, the region comprising amino acids 361-440 in the c-Src kinase domain are required for NF-κB; activation. The same region of c-Src is also required for IL-1-induced IKK activation and the association with IKKγ. Taken together, our results suggest that c-Src plays a critical role in IL-1-induced NF-κB activation through the IKK complex.

KW - c-Src

KW - c-Src KD

KW - IκB-Complex

KW - IKKγ

KW - IL-1-induced NF-κB activation

UR - http://www.scopus.com/inward/record.url?scp=17044362792&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17044362792&partnerID=8YFLogxK

U2 - 10.1093/jb/mvi018

DO - 10.1093/jb/mvi018

M3 - Article

C2 - 15749833

AN - SCOPUS:17044362792

VL - 137

SP - 189

EP - 197

JO - Journal of Biochemistry

JF - Journal of Biochemistry

SN - 0021-924X

IS - 2

ER -