Mouse Neurotrophin 4 (NT-4) E

Neurotrophin-4 (NT-4), also known as NT-5, is a member of the NGF family of neuronal and epithelial growth factors. Neurotrophins have six conserved cysteine residues that are involved in the formation of three disulfide bonds (1 - 3). The mouse NT-4 cDNA encodes a 209 amino acid (aa) precursor that includes a 21 aa signal sequence, a 58 aa propeptide, and a 130 aa mature protein (4,?5). Mouse NT-4 is synthesized as a 28 kDa prepropeptide that is proteolytically processed to generate the mature protein. Mature mouse NT-4 shares 35 - 40% aa sequence identity with mouse beta-NGF, BDNF, and NT-3. It shares 91% and 99% aa sequence identity with human and rat NT-4/5, respectively. The mature protein is secreted as a homodimer and can also form heterodimers with BDNF or NT-3 (6). NT-4 binds and induces receptor dimerization and activation of TrkB (4,?7). NT-4 promotes the development and survival of selected peripheral and CNS neurons (8 - 10). BDNF, which also activates TrkB, overlaps with many but not all NT-4 functions, a distinction that is likely due to differences in expression patterns (8 - 10). NT-4 induced TrkB signaling augments NMDA receptor activity and increases neuronal sensitivity to excitotoxic cell death (11). It also promotes the proliferation of keratinocytes and accelerates hair follicle regression during the follicular cycle (12, 13). NT-4 is secreted by activated T cells and granulocytes at sites of inflammation where it contributes to tissue regeneration (14 - 16).