The neurotrophin receptor family of RTKs include trkA, trkB and trkC (tropomyosin-related kinase) receptors, which respond to NGF, BDNF and neurotrophin-3, respectively. They are associated primarily with proliferative and migration effects in neural systems. Various isoforms of neurotrophin receptors exist, including truncated forms of trkB and trkC, which lack catalytic domains. p75 (TNFRSF16, also known as nerve growth factor receptor), which has homologies with tumour necrosis factor receptors, lacks a tyrosine kinase domain, but can signal via ceramide release and nuclear factor κB (NF-κB) activation. Both trkA and trkB contain two leucine-rich regions and can exist in monomeric or dimeric forms.

[¹²⁵I]NGF (human) and [¹²⁵I]BDNF (human) have been used to label the trkA and trkB receptor, respectively. p75 influences the binding of NGF (NGF, P01138) and neurotrophin-3 (NTF3, P20783) to trkA. The ligand selectivity of p75 appears to be dependent on the cell type; for example, in sympathetic neurones, it binds neurotrophin-3 (NTF3, P20783) with comparable affinity to trkC [5].

Small molecule agonists of trkB have been described, including LM22A4 [7], while ANA12 has been described as a non-competitive antagonist of BDNF binding to trkB [4]. GNF5837 is a family-selective tyrosine kinase inhibitor [1], while the tyrosine kinase activity of the trkA receptor can be inhibited by GW441756 (pIC₅₀= 8.7, [11]) and tyrphostin AG879 [9].

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