Tropomyosin receptor kinase (individual forms: Tropomyosin receptor kinase A, Tropomyosin receptor kinase B, Tropomyosin receptor kinase C) (TrkA (NTRK1), TrkB (NTRK2), TrkC (NTRK3))

The tropomyosin receptor kinase (Trk) family comprises three receptor tyrosine kinases—TrkA, TrkB, and TrkC—encoded by the NTRK1, NTRK2, and NTRK3 genes, respectively. These single-pass transmembrane proteins are critical regulators of neural development and homeostasis, mediating the cellular response to neurotrophins such as nerve growth factor (NGF, for TrkA), brain-derived neurotrophic factor (BDNF, for TrkB), and neurotrophin-3 (NT-3, for TrkC). Ligand binding induces receptor dimerization and autophosphorylation, subsequently activating downstream MAPK and PI3K/AKT pathways essential for neuronal survival, differentiation, and synaptic plasticity. Pathologically, NTRK gene fusions or mutations can drive constitutive kinase activation in a variety of cancers, making these receptors important therapeutic targets with several approved inhibitors (e.g., larotrectinib, entrectinib). Inhibition of these kinases, however, carries risk for neurologic adverse effects due to their role in normal central and peripheral nervous system functions.

Other names

Neurotrophic tyrosine kinase receptor type 1/2/3High affinity nerve growth factor receptor (for TrkA)Tyrosine kinase receptor B/CTRKATRKBTRKCNTRK1NTRK2NTRK3TRK familyTRK1-transforming tyrosine kinase protein (TrkA only)

ATP-competitive inhibition of kinase domain; Blockade of downstream signaling (MAPK, PI3K/AKT pathways); Inhibition of cell proliferation and promotion of apoptosis in tumors harboring NTRK fusions