The tumor necrosis factor (TNF) and TNF receptor (TNFR) gene superfamilies regulate numerous biological functions including cell proliferation, differentiation, and survival through regulating the activation of the transcription factor NF-κB and various mitogen-activated protein kinases. Nerve growth factor receptor (NGFR) was one of the earliest characterized members of this family. Also known as the low-affinity receptor p75NTR, this receptor is involved in several diverse functions such as apoptosis, neurite outgrowth during development, and myelination. Its ligands include NGF, brain-derived neurotrophic factor (BDNF), NT3, and NT4. NGFR can also associate with other NGF receptors such as Trk through the cytosolic and transmembrane domains and thus can function as a co-receptor that refines Trk affinity and specificity for neurotrophins. Finally, upon binding of various neurotrophins, NGFR associates with tumor necrosis factor receptor-6 (TRAF6), suggesting that it can potentially function as a signal transducer for NGF signals through NGFR.
