Cleavage of transmembrane receptors by γ-secretase is the final step in the process of regulated intramembrane proteolysis (RIP) and has a significant impact on receptor function. Although relatively little is known about the molecular mechanism of γ-secretase enzymatic activity, it is becoming clear that substrate dimerization and/or the α-helical structure of the substrate can regulate the si...

In addition to its role as a survival factor, nerve growth factor (NGF) has been implicated in initiating apoptosis in restricted cell types both during development and after terminal cell differentiation. NGF binds to the TrkA tyrosine kinase and the p75 neurotrophin receptor, a member of the tumor necrosis factor cytokine family. To understand the mechanisms underlying survival versus death d...

Nerve growth factor (NGF) receptor-mediated signaling was studied using specific monoclonal antibodies (mAbs) as ligands that discriminate between the receptors TrkA and p75. mAb-induced trophic signals were compared with the signals of the natural ligand NGF. In cells expressing TrkA but no p75 receptors (TrkA+ p75(-)), binding of TrkA with mAb 5C3 leads to optimal signals. In cells expressing...

Alzheimer’s disease is a neurodegenerative disorder characterized by the extracellular deposition in the brain of aggregated b -amyloid peptide, presumed to play a pathogenic role, and by preferential loss of neurons that express the 75-kD neurotrophin receptor (p75 NTR ). Using rat cortical neurons and NIH-3T3 cell line engineered to stably express p75 NTR , we find that the b -amyloid peptide...

We studied the expression of the two tumor necrosis factor (TNF) receptors, p55 and p75, on B cells from patients with chronic lymphocytic leukemia (CLL), and the presence of soluble TNF receptors in serum. Expression of membrane-associated receptors was quantified by double labeling of peripheral blood mononuclear cells (PBMC) with monoclonal antibodies against CD19 and p55/p75 TNF receptors a...

Regulation of cell survival decisions and neuronal plasticity by neurotrophins are mediated by two classes of receptors, Trks (tropomyosin receptor kinases) and p75, the first discovered member of the tumour necrosis factor receptor superfamily. The p75 receptor participates with the TrkA receptor in the formation of high-affinity nerve growth factor-binding sites to promote survival under limi...

NogoA, a myelin-associated component, inhibits neurite outgrowth. Nogo66, a portion of NogoA, binds to Nogo66 receptor (NgR) and induces the inhibitory signaling. LINGO-1 and p75 neurotrophin receptor (p75), the low-affinity nerve growth factor receptor, are also required for NogoA signaling. However, signaling mechanisms downstream to Nogo receptor remain poorly understood. Here, we observed t...

The p75 neurotrophin receptor (p75(NTR)) is a member of the tumor necrosis factor receptor superfamily with a widespread pattern of expression in tissues such as the brain, liver, lung, and muscle. The mechanisms that regulate p75(NTR) transcription in the nervous system and its expression in other tissues remain largely unknown. Here we show that p75(NTR) is an oscillating gene regulated by th...

p75 neurotrophin receptor (p75) regulates diverse functions, including survival, differentiation, growth, and apoptosis of neurons, through its association with a number of molecules. Accumulating evidence shows that βamyloid precursor protein (APP)–related molecules, which also regulate multiple neuronal functions, interact with p75. APP is cleaved by secretases to generate several proteins in...