Tropomyosin receptor kinase B (NTRK2) (TrkB)

Tropomyosin receptor kinase B (TrkB), encoded by the NTRK2 gene, is a high-affinity cell surface receptor for brain-derived neurotrophic factor (BDNF) and is vital for the development and maintenance of the central nervous system [UniProt P17676]. It functions as a receptor tyrosine kinase that, upon ligand binding, undergoes autophosphorylation and activates downstream signaling pathways like MAPK/ERK and PI3K/Akt to promote neuronal survival, differentiation, and synaptic plasticity [PubMed: 12503433]. In the specific context of respiratory physiology, TrkB activation by endogenous BDNF—induced by protocols such as acute intermittent hypoxia (AIH)—is the primary driver of phrenic long-term facilitation (pLTF), a form of motor plasticity that increases phrenic nerve activity and respiratory capacity [PubMed: 20435026, PubMed: 12855749]. This AIH-induced TrkB signaling pathway is a significant area of research for treating respiratory insufficiency in spinal cord injury and Amyotrophic Lateral Sclerosis (ALS) [PubMed: 25630254]. Beyond its role in motor plasticity, TrkB is a major target for antidepressant action and is also a known oncogene when involved in chromosomal translocations, leading to the development of Trk inhibitors for cancer therapy [PubMed: 33446951, PubMed: 25535156]. Small-molecule agonists are being developed to harness TrkB-mediated plasticity for neurorecovery, while kinase inhibitors are used to treat NTRK-positive malignancies [PubMed: 20133810, PubMed: 25535156].

Other names

Neurotrophic tyrosine kinase receptor type 2BDNF/NT-3 growth factor receptorTrk-BNTRK2GP145-TrkB

Agonism of the TrkB receptor to mimic the effects of BDNF for neuroprotection and respiratory plasticity; Inhibition of the TrkB tyrosine kinase domain to block oncogenic signaling in NTRK-fusion positive cancers.