Signaling by NTRK2 (TRKB)

NTRK2 (TRKB) belongs to the family of neurotrophin tyrosine kinase receptors, also known as NTRKs or TRKs. Besides NTRK2, the family includes NTRK1 (TRKA) and NTRK3 (TRKC). Similar to other receptor tyrosine kinases (RTKs), NTRK2 is activated by ligand binding to its extracellular domain. Ligand binding induces receptor dimerization, followed by trans-autophosphorylation of dimerized receptors on conserved tyrosine residues in the cytoplasmic region. Phosphorylated tyrosines in the intracellular domain of the receptor serve as docking sites for adapter proteins, triggering downstream signaling cascaded. Brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NTF4, also known as NT-4) are two high affinity ligands for NTRK2. Neurotrophin-3 (NTF3, also known as NT-3), a high affinity ligand for NTRK3, binds to NTRK2 with low affinity and it is not clear if it the low level of activation of NTRK2 by NTF3 plays a physiologically relevant role. Nerve growth factor (NGF), a high affinity ligand for NTRK1, does not interact with NTRK2. NTRK2 activation triggers downstream RAS, PI3K, and PLCgamma signaling cascades, thought to be involved in neuronal development in both the peripheral (PNS) and central nervous system (CNS). In addition, NTRK2 plays an important, but poorly elucidated, role in long-term potentiation (LTP) and learning (reviewed by Minichiello 2009). NTRK2 may modify neuronal excitability and synaptic transmission by directly phosphorylating voltage gated channels.

Summary from Reactome (R-HSA-9006115), read 2026-09-23.