Selective activation of NF-kappaB by nerve growth factor through the neurotrophin receptor p75

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) selectively bind to distinct members of the Trk family of tyrosine kinase receptors, but all three bind with similar affinities to the neurotrophin receptor p75 ([p75.sup.NTR]). The biological significance of neurotrophin binding to [p75.sup.NTR] in cells that also express Trk receptors has been difficult to ascertain. In the absence of TrkA, NGF binding to [p75.sup.NTR] activated the transcription factor nuclear factor kappa B (NF-kB) in rat Schwann cells. This activation was not observed in Schwann cells isolated from mice that lacked [p75.sup.NTR]. The effect was selective for NGF; NF-kB was not activated by BDNF or NT-3.
The best established role for neurotrophins, which include NGF, BDNF, NT-3, NT-4/5, and NT-6, is their ability to support the survival and differentiation of neurons. Three tyrosine kinase receptors, referred [...]