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

Overview

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.

publication date

  • January 22, 2001

Research

keywords

  • Carrier Proteins
  • NF-kappa B
  • Nerve Growth Factor
  • Protein Kinase C

Identity

Scopus Document Identifier

  • 0035896518

Digital Object Identifier (DOI)

  • 10.1074/jbc.C000869200

PubMed ID

  • 11244088

Additional Document Info

volume

  • 276

issue

  • 11