Trk-C

The neurotrophins, including NGF, BDNF, NT3 and NT4/5, constitute a group of structurally related, secreted proteins that play an important role in the development and function of the nervous system. The biological activities of the neurotrophins are mediated by binding to and activating two unrelated receptor types: the p75 neurotrophin receptor (p75NTR) and the Trk family of receptor tyrosine kinases. p75NTR is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and has been designated TNFRSF16. It binds all neurotrophins with low affinity to transduce cellular signaling pathways that synergize or antagonize those activated by the Trk receptors. Three Trk family proteins, TrkA, TrkB, and TrkC, exhibiting different ligand specificities, have been identified. TrkA binds NGF and NT3, TrkB binds BDNF, NT3 and NT4/ 5, and TrkC only binds NT3. All Trk family proteins share a conserved, complex subdomain organization consisting of a signal peptide, two cysteinerich domains, a cluster of three leucine-rich motifs, and two immunoglobulinlike domains in the extracellular region, as well as an intracellular region that contains the tyrosine kinase domain. Natural splice variants of the different Trks, lacking the first cysteine-rich domain, the first and second or all three of the leucine-rich motifs, or the tyrosine kinase domain, have been described. At the protein sequence level, Trks are highly conserved between species with the extracellular domains of human and mouse TrkC showing 94% amino acid sequence identity. The proteins also exhibit cross-species activity. The primary location of TrkC expression is in the nervous system and, specifically, in regions of the CNS. Low level TrkC expression has also been observed in a wide variety of tissues outside the nervous system.