Structural and Functional Properties of the TRK Family of Neurotrophin Receptors

The Trk family of tyrosine-protein kinases, TrkA, TrkB, and TrkC, are the signaling receptors that mediate the biological properties of the NGF family of neurotrophins. This family of growth factors includes in addition to NGF, BDNF, NT-3, and NT-4. TrkA is the NGF receptor. TrkB serves as a receptor for both BDNF and NT-4, and TrkC is the primary receptor for NT-3. NT-3 is a somewhat promiscuous ligand that can also activate TrkA and TrkB receptors at high concentrations. The trkB and trkC genes also encode noncatalytic receptor isoforms of an, as yet, unknown function. In addition to the Trk receptors, the NGF family of neurotrophins also binds with low affinity to an unrelated molecule, designated p75, a member of the TNF-receptor superfamily. Recently, we have generated strains of mice lacking each of these tyrosine-kinase receptors by gene targeting in embryonic stem cells. Characterization of these mutant mice is providing relevant information regarding the critical role that these receptors play in the ontogeny of the mammalian nervous system.