Tumor necrosis factor (TNF) receptor 1 signaling downstream of TNF receptor-associated factor 2. Nuclear factor κB (NFκB)-inducing kinase requirement for activation of activating protein 1 and NFκB but not of c- Jun N-terminal kinase/stress-activated protein kinase

Gioacchino Natoli, Antonio Costanzo, Francesca Moretti, Marcella Fulco, Clara Balsano, Massimo Levrero

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Like other members of the tumor necrosis factor (TNF) receptor family, p55 TNF receptor 1 (TNF-R1) lacks intrinsic signaling capacity and transduces signals by recruiting associating molecules. The TNF-R1 associated death domain protein interacts with the p55 TNF-R1 cytoplasmic domain and recruits the Fas-associated death domain protein (which directly activates the apoptotic proteases), the protein kinase receptor interacting protein, and TNF receptor-associated factor 2 (TRAF2). TRAF2 has previously been demonstrated to activate both transcription factor nuclear factor κB (NFκB) and the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway, which in turn stimulates transcription factor activating protein 1 (AP1) mainly via phosphorylation of the c-Jun component. We have investigated the signaling properties of NFκB-inducing kinase (NIK), a TRAF2-associated protein kinase that mediates NFκB induction. NIK was found to be unable to activate JNK/SAPK, mitogen-activated protein kinase, or p38 kinase. Moreover, NIK was not required for JNK/SAPK activation by TNF-R1, thus representing the first TNF-R1 complex component to dissect the NFκB and the JNK/SAPK pathways. Despite being unable to activate JNK/SAPK and mitogen-activated protein kinase, NIK strongly activated AP1 and was required for TNF-R1- induced AP1 activation. Therefore, NIK links TNF-R1 to a novel, JNK/SAPK- independent, AP1 activation pathway.

Original languageEnglish
Pages (from-to)26079-26082
Number of pages4
JournalJournal of Biological Chemistry
Volume272
Issue number42
DOIs
Publication statusPublished - Oct 17 1997

Fingerprint

Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
JNK Mitogen-Activated Protein Kinases
Tumor Necrosis Factor Receptors
Nuclear Proteins
Heat-Shock Proteins
Protein Kinases
Phosphotransferases
Chemical activation
Tumor Necrosis Factor-alpha
Proteins
TNF Receptor-Associated Factor 2
Activating Transcription Factor 1
Fas-Associated Death Domain Protein
Activating Transcription Factors
Receptor-Interacting Protein Serine-Threonine Kinases
MAP Kinase Kinase Kinases
Phosphorylation
p38 Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Peptide Hydrolases

ASJC Scopus subject areas

  • Biochemistry

Cite this

@article{94fb61703de4440689483af170a1687f,
title = "Tumor necrosis factor (TNF) receptor 1 signaling downstream of TNF receptor-associated factor 2. Nuclear factor κB (NFκB)-inducing kinase requirement for activation of activating protein 1 and NFκB but not of c- Jun N-terminal kinase/stress-activated protein kinase",
abstract = "Like other members of the tumor necrosis factor (TNF) receptor family, p55 TNF receptor 1 (TNF-R1) lacks intrinsic signaling capacity and transduces signals by recruiting associating molecules. The TNF-R1 associated death domain protein interacts with the p55 TNF-R1 cytoplasmic domain and recruits the Fas-associated death domain protein (which directly activates the apoptotic proteases), the protein kinase receptor interacting protein, and TNF receptor-associated factor 2 (TRAF2). TRAF2 has previously been demonstrated to activate both transcription factor nuclear factor κB (NFκB) and the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway, which in turn stimulates transcription factor activating protein 1 (AP1) mainly via phosphorylation of the c-Jun component. We have investigated the signaling properties of NFκB-inducing kinase (NIK), a TRAF2-associated protein kinase that mediates NFκB induction. NIK was found to be unable to activate JNK/SAPK, mitogen-activated protein kinase, or p38 kinase. Moreover, NIK was not required for JNK/SAPK activation by TNF-R1, thus representing the first TNF-R1 complex component to dissect the NFκB and the JNK/SAPK pathways. Despite being unable to activate JNK/SAPK and mitogen-activated protein kinase, NIK strongly activated AP1 and was required for TNF-R1- induced AP1 activation. Therefore, NIK links TNF-R1 to a novel, JNK/SAPK- independent, AP1 activation pathway.",
author = "Gioacchino Natoli and Antonio Costanzo and Francesca Moretti and Marcella Fulco and Clara Balsano and Massimo Levrero",
year = "1997",
month = "10",
day = "17",
doi = "10.1074/jbc.272.42.26079",
language = "English",
volume = "272",
pages = "26079--26082",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "42",

}

TY - JOUR

T1 - Tumor necrosis factor (TNF) receptor 1 signaling downstream of TNF receptor-associated factor 2. Nuclear factor κB (NFκB)-inducing kinase requirement for activation of activating protein 1 and NFκB but not of c- Jun N-terminal kinase/stress-activated protein kinase

AU - Natoli, Gioacchino

AU - Costanzo, Antonio

AU - Moretti, Francesca

AU - Fulco, Marcella

AU - Balsano, Clara

AU - Levrero, Massimo

PY - 1997/10/17

Y1 - 1997/10/17

N2 - Like other members of the tumor necrosis factor (TNF) receptor family, p55 TNF receptor 1 (TNF-R1) lacks intrinsic signaling capacity and transduces signals by recruiting associating molecules. The TNF-R1 associated death domain protein interacts with the p55 TNF-R1 cytoplasmic domain and recruits the Fas-associated death domain protein (which directly activates the apoptotic proteases), the protein kinase receptor interacting protein, and TNF receptor-associated factor 2 (TRAF2). TRAF2 has previously been demonstrated to activate both transcription factor nuclear factor κB (NFκB) and the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway, which in turn stimulates transcription factor activating protein 1 (AP1) mainly via phosphorylation of the c-Jun component. We have investigated the signaling properties of NFκB-inducing kinase (NIK), a TRAF2-associated protein kinase that mediates NFκB induction. NIK was found to be unable to activate JNK/SAPK, mitogen-activated protein kinase, or p38 kinase. Moreover, NIK was not required for JNK/SAPK activation by TNF-R1, thus representing the first TNF-R1 complex component to dissect the NFκB and the JNK/SAPK pathways. Despite being unable to activate JNK/SAPK and mitogen-activated protein kinase, NIK strongly activated AP1 and was required for TNF-R1- induced AP1 activation. Therefore, NIK links TNF-R1 to a novel, JNK/SAPK- independent, AP1 activation pathway.

AB - Like other members of the tumor necrosis factor (TNF) receptor family, p55 TNF receptor 1 (TNF-R1) lacks intrinsic signaling capacity and transduces signals by recruiting associating molecules. The TNF-R1 associated death domain protein interacts with the p55 TNF-R1 cytoplasmic domain and recruits the Fas-associated death domain protein (which directly activates the apoptotic proteases), the protein kinase receptor interacting protein, and TNF receptor-associated factor 2 (TRAF2). TRAF2 has previously been demonstrated to activate both transcription factor nuclear factor κB (NFκB) and the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway, which in turn stimulates transcription factor activating protein 1 (AP1) mainly via phosphorylation of the c-Jun component. We have investigated the signaling properties of NFκB-inducing kinase (NIK), a TRAF2-associated protein kinase that mediates NFκB induction. NIK was found to be unable to activate JNK/SAPK, mitogen-activated protein kinase, or p38 kinase. Moreover, NIK was not required for JNK/SAPK activation by TNF-R1, thus representing the first TNF-R1 complex component to dissect the NFκB and the JNK/SAPK pathways. Despite being unable to activate JNK/SAPK and mitogen-activated protein kinase, NIK strongly activated AP1 and was required for TNF-R1- induced AP1 activation. Therefore, NIK links TNF-R1 to a novel, JNK/SAPK- independent, AP1 activation pathway.

UR - http://www.scopus.com/inward/record.url?scp=0030666194&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030666194&partnerID=8YFLogxK

U2 - 10.1074/jbc.272.42.26079

DO - 10.1074/jbc.272.42.26079

M3 - Article

C2 - 9334169

AN - SCOPUS:0030666194

VL - 272

SP - 26079

EP - 26082

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 42

ER -