The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor.

TitleThe atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor.
Publication TypeJournal Article
Year of Publication2001
AuthorsWooten MW, Seibenhener ML, Mamidipudi V, Diaz-Meco MT, Barker PA, Moscat J
JournalJ Biol Chem
Volume276
Issue11
Pagination7709-12
Date Published2001 Mar 16
ISSN0021-9258
KeywordsAnimals, Carrier Proteins, Cells, Cultured, Humans, Nerve Growth Factor, NF-kappa B, PC12 Cells, Protein Kinase C, Rats, Receptor, Nerve Growth Factor, Receptor, trkA
Abstract

Nerve growth factor (NGF) binding to both p75 and TrkA neurotrophin receptors activates the transcription factor nuclear factor kappaB (NF-kappaB). Here we show that the atypical protein kinase C-interacting protein, p62, which binds TRAF6, selectively interacts with TrkA but not p75. In contrast, TRAF6 interacts with p75 but not TrkA. We demonstrate the formation of a TRAF6-p62 complex that serves as a bridge linking both p75 and TrkA signaling. Of functional relevance, transfection of antisense p62-enhanced p75-mediated cell death and diminished NGF-induced differentiation occur through a mechanism involving inhibition of IKK activity. These findings reveal a new function for p62 as a common platform for communication of both p75-TRAF6 and TrkA signals. Moreover, we demonstrated that p62 serves as a scaffold for activation of the NF-kappaB pathway, which mediates NGF survival and differentiation responses.

DOI10.1074/jbc.C000869200
Alternate JournalJ Biol Chem
PubMed ID11244088
Related Faculty: 
Jorge Moscat, Ph.D. Maria Diaz-Meco Conde, Ph.D.

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