Mw. Wooten et al., The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappa B activation by nerve growth factor, J BIOL CHEM, 276(11), 2001, pp. 7709-7712
Nerve growth factor (NGF) binding to both p75 and TrkA neurotrophin recepto
rs activates the transcription factor nuclear factor kappaB (NF-kappaB). He
re we show that the atypical protein kinase C-interacting protein, p62, whi
ch binds TRAF6, selectively interacts with TrkA but not p75. In contrast, T
RAF6 interacts with p75 but not TrkA. We demonstrate the formation of a TRA
F6-p62 complex that serves as a bridge linking both p75 and TrkA signaling.
Of functional relevance, transfection of antisense p62-enhanced p75-mediat
ed cell death and diminished NGF-induced differentiation occur through a me
chanism involving inhibition of IKK activity. These findings reveal a new f
unction for p62 as a common platform for communication of both p75-TRAF6 an
d TrkA signals. Moreover, we demonstrated that p62 serves as a scaffold for
activation of the NF-kappaB pathway, which mediates NGF survival and diffe
rentiation responses.