TRKs

TRKs, or Tropomyosin Receptor Kinases, are a family of receptor tyrosine kinases crucial for the development and function of the nervous system. They are encoded by the NTRK genes, specifically NTRK1, NTRK2, and NTRK3, which correspond to TRKA, TRKB, and TRKC, respectively. These receptors are activated by neurotrophins, a group of secreted proteins that promote the survival, differentiation, and growth of neurons.

TRKA binds to Nerve Growth Factor (NGF), TRKB binds to Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin-4/5 (NT-4/5), and TRKC binds to Neurotrophin-3 (NT-3). Upon binding of their respective neurotrophins, TRKs dimerize and undergo autophosphorylation, initiating intracellular signaling cascades. These pathways regulate gene expression involved in neuronal plasticity, synapse formation, and overall neuronal health.

Dysregulation of TRK signaling has been implicated in various neurological disorders and diseases, including cancer. In certain cancers, the NTRK genes can undergo fusion events, leading to the production of constitutively active TRK fusion proteins. These aberrant proteins drive tumor growth and metastasis, making them attractive targets for targeted cancer therapies. Inhibitors that block TRK activity have shown promise in treating cancers harboring NTRK fusions. Understanding the intricate roles of TRKs in both physiological and pathological contexts continues to be an active area of research.