The neurotrophin family of signaling factors comprise nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophins NT-3 and NT-4. These factors are involved in the differentiation and survival of neural cells. The best characterized receptors for these trophic factors are the tropomyosin-related tyrosine kinase receptors TrkA, TrkB, and TrkC, and a member of the tumor necrosis factor receptor family, NGFR (p75NTR). Neurotrophin/Trk signaling is regulated by connecting to a variety of intracellular signaling cascades including the MAPK, PI-3 kinase and PLC pathways, transmitting positive signals like enhanced survival and growth. In contrast, signaling via the p75NTR receptor transmits both positive and negative signals. These signals play an important role for neural development and additional higher-order activities such as learning and memory.
The tyrosine kinase receptors have different affinities for the different neurotrophic factors. TrkA is a high-affinity receptor for NGF while TrkB is a high-affinity receptor for BDNF and NT-4, TrkC is a high-affinity receptor for NT-3. NGFR binds NGF, BDNF, NT-3, and NT-4, in combination with Sortilin, a co-receptor for NGF.
The NGFR receptor has been repeatedly implicated in neuronal death. Apoptosis of neuronal cell lines, glia and a variety of primary neurons in vitro is mediated by ligand activation of NGFR. Sortilin is expressed in a wide variety of tissues, but is most abundant in the central nervous system during development and in adults. NGFR and Sortilin form a receptor complex that binds NGF at the cell surface. Both receptors appear to be required to transduce apoptotic effects.
It seems unlikely, that neurotrophin receptors have such opposite effects on neuronal survival and act independently, as each receptor can engage survival-promoting or death-promoting signaling pathways. Although there is evidence of crosstalk between signaling pathways engaged by NGFR and Trk receptors, the mechanisms are not well understood and much remains to be uncovered in this exciting field of research.
Selected Antibodies for Neurotrophin family signaling:
- NTF4 12297-1-AP (Rabbit polyclonal)
- NTF3 18084-1-AP (Rabbit polyclonal)
- NTRK2 13129-1-AP (Rabbit polyclonal)
- NTRK3 11999-1-AP (Rabbit polyclonal)
- CSK 17720-1-AP (Rabbit polyclonal)
- IRS1 17509-1-AP (Rabbit polyclonal)
- FRS2 11503-1-AP (Rabbit polyclonal)
- CRK 16685-1-AP (Rabbit polyclonal)
- TRAF6 12809-1-AP (Rabbit polyclonal)
- ATF4 10835-1-AP (Rabbit polyclonal)
- ATF4 60035-1-Ig (Mouse monoclonal)