The insulin receptor-related receptor (IRR) has recently been identified as a member of the insulin receptor tyrosine kinase family; however, its endogenous ligand and biological function are still unknown. In contrast to the very widespread pattern of expression of the homologous insulin and IGF-I receptors, IRR demonstrates a very restricted cellular distribution. Using in situ hybridization ...

Ligand-induced receptor oligomerization is an established mechanism for receptor tyrosine kinase activation. However, numerous receptor tyrosine kinases are expressed in multicomponent complexes with other receptors that may signal independently or alter the binding characteristics of the receptor tyrosine kinase. NGF interacts with two structurally unrelated receptors, the Trk A receptor tyros...

Neurotrophins (NTs) induce gene transcription by binding their high-affinity tropomyosin-related kinase (Trk) receptors and initiating intracellular signal transduction cascades. In particular, activation of the cyclic AMP response element (CRE) in the promoters of target genes serves as surrogate markers for Trk receptor activation as demonstrated in both in vivo and in vitro systems. We used ...

The TRK-T1 oncogene, isolated from a human thyroid carcinoma, represents a rearranged form of the high affinity nerve growth factor (NGF) receptor encoded by the NTRK1 gene; it is created by an intrachromosomal rearrangement fusing the NTRK1 tyrosine kinase domain to the 5' portion of the TPR gene. We have investigated the effect of the TRK-T1 oncogene in PC12 cells, a model system for studying...

Objective Fusions involving neurotrophic tyrosine receptor kinase ( NTRK ) are known oncogenic drivers in a broad range of tumor types. It recently gained attention as predictor targeted therapy since selective inhibitors now approved the US and Europe for patients with solid tumors harboring gene fusions. However, estimation fusion/alteration frequency its clinicopathological characteristics p...

Although neurotrophin actions in the survival of specific retinal cell types have been identified, the biological functions for neurotrophin-3 (NT-3) in early retinal development remain unclear. Having localized NT-3 and trk C expression at early developmental stages when retinal neuroepithelial progenitor cells predominate, we sought to modulate NT-3 signaling in these cells by overexpressing ...

Tropomyosin receptor kinase (TRK) represents an attractive oncology target for cancer therapy related to its critical role in formation and progression. NTRK fusions are found occur 3.3% of lung cancers, 2.2% colorectal 16.7% thyroid 2.5% glioblastomas, 7.1% pediatric gliomas. In this paper, we described the discovery type-II pan-TRK inhibitor 4c through structure-based drug design strategy fro...

Neuroblastomas (NBs) with favorable outcome usually express TrkA, whereas unfavorable NBs frequently express TrkB and its cognate ligand BDNF. P75 (p75(LNTR), NGFR, TNFRSF16) binds NGF-related neurotrophins with low affinity and usually is coexpressed with Trk receptors in NBs. Here, we investigated the importance of p75 coexpression with Trk receptors in NBs. We transfected p75 into two Trk-nu...

Genetic and pharmacological perturbations suggest that tyrosine receptor kinase B (trkB) receptor activation promotes limbic epileptogenesis, but whether or where trkB activation occurs during epileptogenesis is uncertain. Because activation of trk receptors involves phosphorylation of specific tyrosine residues (Segal et al., 1996), the availability of antibodies that selectively recognize the...

The distributions of mRNAs for the protooncogene trk and the low-affinity NGF receptor (LNGFR) were studied by hybridization with oligonucleotide probes on sections of adult rat primary sensory and sympathetic ganglia. For comparison with high-affinity binding sites, adjacent sections were processed for NGF receptor radioautography. Among neurons in lumbar dorsal root ganglia and trigeminal gan...