Selective Activation of NF-κB by Nerve Growth Factor Through the Neurotrophin Receptor p75

Abstract
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 NTR ). The biological significance of neurotrophin binding to p75 NTR in cells that also express Trk receptors has been difficult to ascertain. In the absence of TrkA, NGF binding to p75 NTR activated the transcription factor nuclear factor kappa B (NF-κB) in rat Schwann cells. This activation was not observed in Schwann cells isolated from mice that lacked p75 NTR . The effect was selective for NGF; NF-κB was not activated by BDNF or NT-3.