Neurotrophin-mediated cell survival and differentiation of vertebrate neurons is caused by ligand-specific binding to the Trk family of tyrosine kinase receptors. However, sites in the neurotrophins responsible for the binding to Trk receptors and the mechanisms whereby this interaction results in receptor activation and biological activity are unknown. Here we show that in nerve growth factor ...

Tyrosine phosphorylation of beta-catenin, a component of adhesion complexes and of the Wnt pathway, affects cell adhesion, migration and gene transcription. By reducing beta-catenin availability using shRNA-mediated gene silencing or expression of intracellular N-cadherin, we show that beta-catenin is required for axon growth downstream of brain-derived neurotrophic factor (BDNF) signalling and...

In this study, we have shown that nerve growth factor (NGF)-dependent activation of the p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) pathway in PC12 cells can be partially blocked by pertussis toxin (which inactivates the G proteins G(i/o)). This suggests that the Trk A receptor may use a G protein-coupled receptor pathway to signal to p42/p44 MAPK. This was supported by data showing...

Calcific aortic valve disease (CAVD) is a leading cardiovascular disorder in the elderly. Diseased aortic valves are characterized by sclerosis (fibrosis) and nodular calcification. Sclerosis, an early pathological change, is caused by aortic valve interstitial cell (AVIC) proliferation and overproduction of extracellular matrix (ECM) proteins. However, the mechanism of aortic valve sclerosis r...

There is growing evidence that reduced neurotrophic support is a significant factor in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). In this review we discuss the structure and functions of neurotrophins such as nerve growth factor, and the role of these proteins and their tyrosine kinase (Trk) ...

Brain-derived neurotrophic factor (BDNF) is one of neurotrophins involved in the development and maintenance of both the peripheral nervous system and CNS. Although the expression of BDNF and its receptor TrkB still occurs in the adult stage, their physiological role in the mature CNS is not fully understood. In the present study we examined in detail the possibility that BDNF modulates synapti...

Localization of Trk neurotrophin receptors is an important factor in directing cellular communication in developing and mature neurons. One potential site of action is in lipid raft membrane microdomains. Although Trk receptors have been localized to lipid rafts, little is known about how these neurotrophin receptors are directed there or how localization to these membrane microdomains regulate...

UNLABELLED The use of high-throughput next-generation sequencing techniques in multiple tumor types during the last few years has identified NTRK1, 2, and 3 gene rearrangements encoding novel oncogenic fusions in 19 different tumor types to date. These recent developments have led us to revisit an old oncogene, Trk (originally identified as OncD), which encodes the TPM3-NTRK1 gene fusion and wa...

NGF binds to and activates the protein tyrosine kinase gp 140prototrk. Expression of this receptor is required for at least some responses to NGF. Three outstanding issues are addressed in the present work. First, we determined whether expression of gp 140prototrk is required for all neuronal NGF responses. Second, we examined the role of gp 140prototrk in NGF binding and internalization. Third...

We evaluated the effect of a stable synthetic prostacyclin analogue, TRK-100, on the microcirculatory derangement occurring in feline pial vessels with endothelial damage after middle cerebral artery occlusion. Fifteen adult cats were divided into an untreated group (Group 1, n = 8) and a treated group (Group 2, n = 7). Thirty minutes after 10 minutes of ultraviolet irradiation, which selective...