Trk receptors are a family of tyrosine kinases that regulates synaptic strength and plasticity in the mammalian nervous system.
The common ligands of trk receptors are neurotrophins, a family of growth factors critical to the functioning of the nervous system.
[5] The oncogene was generated by a mutation in chromosome 1 that resulted in the fusion of the first seven exons of tropomyosin to the transmembrane and cytoplasmic domains of the then-unknown TrkA receptor.
The differences in the signaling initiated by these distinct types of receptors are important for generating diverse biological responses.
[6] NGF is a neurotrophic factor, and the NGF/TrkA interaction is critical in both local and nuclear actions, regulating growth cones, motility, and expression of genes encoding the biosynthesis of enzymes for neurotransmitters.
The TrkA receptor is associated with several diseases such as Inflammatory arthritis, keratoconus, functional dyspepsia and, in some cases, over expression has been linked to cancer development.
[8][9][10] In other cases, such as neuroblastoma Trk A acts as a promising prognostic indicator as it has the potential to induce terminal differentiation of cancer cells in a context-dependent manner.
BDNF is a growth factor that has important roles in the survival and function of neurons in the central nervous system.
The binding of BDNF to TrkB receptor causes many intracellular cascades to be activated, which regulate neuronal development and plasticity, long-term potentiation, and apoptosis.
[3] Therefore, the data suggest that the presence of p75NTR affects the conformation of TrkA, preferentially the state with high-affinity binding site for NGF.
[16] BDNF belongs to the neurotrophin family of growth factors and affects the survival and function of neurons in the central nervous system, particularly in brain regions susceptible to degeneration in AD.
[15] Increased NT-3/trkC binding results in larger monosynaptic excitatory postsynaptic potentials (EPSPs) and reduced polysynaptic components.
[15] In the development of mammalian visual system, axons from each eyes crosses through the lateral geniculate nucleus (LGN) and terminate in separate layers of striate cortex.
However, A study demonstrated that the infusion of NT-4 (a ligand of trkB) into the visual cortex during the critical period has been shown to prevent many consequences of monocular deprivation.
[18] More specifically, differential expression of Trk receptors closely correlates to prognosis and outcome in a number of cancers, such as neuroblastoma.
[citation needed] As a result, Trk inhibitors have been explored as a potential treatment avenue in the field of precision medicine.
[citation needed] Trk inhibitors are (in 2015) in clinical trials and have shown early promise in shrinking human tumors.
[20] Originally targeting soft tissue sarcomas, Larotrectinib (tradename Vitrakvi) was approved in November 2018 as a tissue-agnostic inhibitor of TrkA, TrkB, and TrkC developed by Array BioPharma for solid tumors with NTRK fusion mutations.
[21] Due to this development of effective TRK inhibitors, the European Society for Medical Oncology (ESMO) is recommending that testing for NTRK fusion mutations is performed in the work up for non small cell lung cancer.
[3] Phosphorylation of tyrosine residues in the Trk receptors led to the activation of Ras molecules, H-Ras and K-Ras.