TrkB

TrkB, short for tropomyosin receptor kinase B, is a receptor tyrosine kinase belonging to the neurotrophin receptor family. In humans it is encoded by the NTRK2 gene. TrkB is expressed primarily in the central and peripheral nervous systems, with high levels in regions such as the hippocampus and cortex that are involved in learning and memory.

TrkB is activated by binding of brain-derived neurotrophic factor (BDNF) and, at lower affinity, neurotrophin-4/5 (NT-4/5). Ligand binding promotes receptor dimerization and autophosphorylation of tyrosine residues in the juxtamembrane and kinase domains, creating docking sites for adaptor proteins and triggering signaling cascades. The major pathways engaged include Ras-MAPK, PI3K-Akt, and PLCγ, which collectively promote neuronal survival, differentiation, dendritic growth, synaptic plasticity, and long-term potentiation.

TrkB has several isoforms produced by alternative splicing. The full-length receptor contains an intracellular tyrosine kinase domain essential for canonical signaling, whereas truncated isoforms such as TrkB.T1 and TrkB.T-Shc lack kinase activity and can modulate signaling through kinase-independent mechanisms or by interacting with other proteins.

Biological roles of TrkB include guiding neuronal maturation and circuit formation during development, and supporting synaptic plasticity, learning, and mood regulation in the adult brain. Dysregulation of TrkB signaling has been linked to neuropsychiatric disorders and neurodegenerative diseases. In cancer, NTRK2 gene fusions or overexpression can contribute to tumorigenesis in rare cases, and TRK inhibitors are approved for tumors carrying NTRK fusions, including those involving NTRK2.

Research into TrkB continues with exploration of selective agonists, biased signaling, and strategies to enhance TrkB signaling for aging and neurodegenerative conditions.