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

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

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ASJC Scopus subject areas

  • Biochemistry

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