Tropomyosin receptor kinase B (TrkB)

Tropomyosin receptor kinase B (TrkB) is a high-affinity catalytic receptor for several neurotrophins—most notably brain-derived neurotrophic factor (BDNF)—and is encoded by the NTRK2 gene. It belongs to the family of receptor tyrosine kinases. Upon binding its ligand BDNF (as well as NT‑4/5), TrkB dimerizes and undergoes autophosphorylation at specific intracellular tyrosines. This triggers activation of major intracellular signaling pathways including MAPK/ERK, PI3K/Akt, and PLCγ/Ca²⁺ cascades that regulate neuronal survival, differentiation, synaptic plasticity, dendritic morphology changes—and in non-neuronal contexts such as cancer cells—cell proliferation and invasiveness[1][3][5]. The canonical full-length isoform contains an extracellular ligand-binding domain with immunoglobulin-like regions conferring specificity for BDNF; a single transmembrane region; and an intracellular tyrosine kinase domain responsible for signal transduction upon activation[1]. Alternative splicing produces truncated isoforms lacking full signaling capacity but potentially modulating cellular responses. The biological importance of the BDNF–TrkB axis extends from CNS development to adult neural maintenance; dysregulation has been implicated in various pathologies including cancers where it promotes tumor aggressiveness,[2][4] psychiatric disorders such as depression,[8] schizophrenia,[7] as well as neurodegenerative conditions like ALS or multiple sclerosis.[6] Therapeutic strategies are being explored both to enhance activity where beneficial—for example in depression—or inhibit it where pathological—for example in certain tumors.[2][4]

Other names

Tyrosine receptor kinase BNeurotrophic tyrosine kinase, receptor, type 2NTRK2 (gene name)BDNF/NT-3 growth factors receptor

Drugs or molecules targeting this pathway typically act by inhibiting the binding of brain-derived neurotrophic factor (BDNF) to TrkB or blocking the downstream signaling cascades activated by TrkB autophosphorylation. This can suppress cell survival signals in cancer or modulate neuronal plasticity in neurological diseases[1][3][4].