The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor.
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.
Wooten
M W
MW
Department of Biological Sciences, Program in Cell and Molecular Biosciences, Auburn University, Auburn, Alabama 36849, USA. wootemw@auburn.edu
Seibenhener
M L
ML
Mamidipudi
V
V
Diaz-Meco
M T
MT
Barker
P A
PA
Moscat
J
J
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000502:physiology*; D016716:PC12 Cells; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D020800:Receptor, Nerve Growth Factor / Q000502:physiology; D020917:Receptor, trkA / Q000502:physiology
D002352:Carrier Proteins; D016328:NF-kappa B; D020800:Receptor, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D011493:Protein Kinase C