Tropomyosin receptor kinase A, B, and C (TrkA, TrkB, TrkC)

Tropomyosin receptor kinases A, B, and C (TrkA, TrkB, TrkC) are a family of single-pass transmembrane receptor tyrosine kinases that serve as high-affinity receptors for neurotrophins. Each subtype has a preferred ligand: TrkA binds nerve growth factor (NGF), TrkB binds brain-derived neurotrophic factor (BDNF) and neurotrophin‑4 (NT‑4), while TrkC primarily binds neurotrophin‑3 (NT‑3). Upon ligand binding, these receptors dimerize and autophosphorylate their intracellular domains, activating multiple downstream signaling cascades including Ras/MAPK and PI3K/Akt pathways. These signals regulate neuronal survival, differentiation, synaptic plasticity, cell proliferation, motility, apoptosis avoidance—and play critical roles in both development and maintenance of the nervous system. Genetic alterations such as fusions or mutations involving the genes encoding these receptors (NTRK1, NTRK2, NTRK3) have been implicated in various cancers by driving constitutive activation independent of ligand binding. As a result they are important therapeutic targets; several selective inhibitors have been developed specifically targeting tumors harboring such alterations. Beyond oncology they are also involved in rare congenital neurological disorders when mutated or dysfunctional.

Other names

Neurotrophic tyrosine kinase receptor type 1 (TrkA)Neurotrophic tyrosine kinase receptor type 2 (TrkB)Neurotrophic tyrosine kinase receptor type 3 (TrkC)NTRK1 (gene for TrkA)NTRK2 (gene for TrkB)NTRK3 (gene for TrkC)High affinity nerve growth factor receptorTRK1-transforming tyrosine kinase protein

Inhibition of the intracellular tyrosine kinase domain to block downstream neurotrophin signaling pathways such as Ras/MAPK and PI3K/Akt