Disease relevance of NGFR

• To generate a human central nervous system neuronal cell line that would respond to NGF, we infected the medulloblastoma cell line D283 MED with a defective retrovirus carrying the cDNA coding for the human NGFR [1].
• Human nerve growth factor (NGF) receptor (NGFR) cDNA was transfected into a neuroblastoma cell line (HTLA 230) which does not express a functional NGF-NGFR signal transduction cascade [2].
• Thirteen of thirty-five CNS PNETs showed NGFR positivity [3].
• In PNS neuroectodermal tumors, there was NGFR expression in tumor cells of 6 of 11 neuroblastomas and 6 of 6 ganglioneuroblastomas or ganglioneuromas [3].
• In this study, NGFR expression by human fetal and adult adrenal medullary tissue, peripheral nervous system (PNS) neuroectodermal tumors (neuroblastoma, ganglioneuroblastoma, ganglioneuroma), pediatric primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS), and CNS gliomas was examined by an immunohistochemical technique [3].

Psychiatry related information on NGFR

• NGF receptor gene expression is decreased in the nucleus basalis in Alzheimer's disease [4].
• In contrast to AD, NGF receptor-containing cortical neurons were not observed in Parkinson disease, Pick disease, or Shy-Drager syndrome [5].
• A missense polymorphism (S205L) of the low-affinity neurotrophin receptor p75NTR gene is associated with depressive disorder and attempted suicide [6].

High impact information on NGFR

• Surprisingly, the 55 kd TNF receptor shows a high degree of sequence homology to the NGF receptor extracellular domain [7].
• Transfection of a full-length cDNA in mouse fibroblasts results in stable expression of NGF receptors that are recognized by monoclonal antibodies to the human NGF receptor and that bind [125I]NGF [8].
• Induction of apoptosis by the low-affinity NGF receptor [9].
• These results suggest that the NGF receptor system enhances the activities of both the guanine nucleotide exchange factor and GAP and that the activation of Ras might be controlled by the balance in activity between these two regulatory proteins [10].
• Neurite outgrowth was not observed with chimeric receptors that contained the transmembrane domain from the EGFR, suggesting that the membrane-spanning region and cytoplasmic domain of the low-affinity NGFR are necessary for signal transduction [11].

Chemical compound and disease context of NGFR

• Tyrosine kinase inhibitor CEP-701 blocks the NTRK1/NGF receptor and limits the invasive capability of prostate cancer cells in vitro [12].
• Using an antibody to the nerve growth factor receptor (NGFR), we examined dendritic reticulum cells (DRCs) immunohistochemically in 62 formalin-fixed, paraffin-embedded lymph nodes from patients with reactive follicular hyperplasia or with various types of lymphoma [13].
• We have demonstrated that treatment of rat pheochromocytoma (PC12) cells with acetyl-L-carnitine (ALCAR) stimulates the synthesis of nerve growth factor receptors (NGFR) [14].
• Nineteen granular cell tumors (GCT) of adults, two congenital granular cell epulides and five epulides fibrosae were immunohistochemically examined to detect the expression of 75 kDa nerve growth factor receptor (NGFR), trk gene product, phosphotyrosine (PT), protein gene product 9.5 (PGP9.5) and S-100 protein [15].
• The present study was designed to examine (1) if neural neurotrophin targets respond to estrogen as a general phenotypic feature and (2) if NGF receptor mRNAs are regulated by estrogen, using a prototypical target of NGF, the dorsal root ganglion (DRG) (sensory) neuron [16].

Biological context of NGFR

• Using chromosome painting and the NGFR gene as an outside marker, we show that the U2 tandem array (RNU2) has remained at the same chromosomal locus (equivalent to human 17q21) through multiple speciation events over > 35 million years leading to the Old World monkey and hominoid lineages [17].
• Expression of the cloned human nerve growth factor receptor (NGFR) cDNA in cell lines can generate both high- and low-affinity binding sites [1].
• The transformant line LAN5/NGFR expressed both high- and low-affinity NGFRs, displayed NGF-induced up-regulation of fos oncogene, and efficiently internalized NGF [18].
• However, high expression levels of nerve growth factor receptor (NGFR), neural cell adhesion molecule (N-CAM), and cell adhesion molecule L1 (L1) were observed [19].
• Inhibition of NGFR tyrosine phosphorylation had no effect but the src inhibitor PP1 abolished MAPK and Akt phosphorylation in all three clones [20].

Anatomical context of NGFR

• Moreover, we showed that gp140trk tyrosine kinase, which serves as an NGFR, was involved in transduction of early signaling events in human B lymphocytes [21].
• Osmopump delivery prevented the decline of NGFR-TrkA, insulin receptor (P < 0.05), and IGF-IR (P < 0.005) expressions in DRGs and improved NGF content (P < 0.05) in sciatic nerve [22].
• We examined changes in immunostaining for NGFR in chromaffin cells cultured for 4 weeks in the presence or absence of NGF, with or without dexamethasone (DEX), which inhibits neuritic outgrowth from these cells [23].
• Immunohistochemical analysis showed that NGFR is expressed in several nonneural human tissues, and the cell types in which NGFR was found include derivatives from all three germ layers [24].
• In addition to cell lines derived from neuroblastoma, astrocytoma, and melanoma, all of which share a common neuroectodermal origin, NGFR was detected in a number of cultured cells of mesenchymal, epithelial, and hematopoietic derivation [24].

Associations of NGFR with chemical compounds

• Its action is mediated by a specific cell surface transmembrane glycoprotein, nerve growth factor receptor (NGFR) [3].
• Also, the expression of different species of NGFR could be modified by treatment with retinoic acid (RA) [25].
• NGFR expression in invasive tumours significantly correlated with that of cytokeratins 5/6 (P<0.05), 14 (P<0.0001) and 17 (P<0.0005) and EGFR (P<0.0001) and displayed an inverse correlation with oestrogen and progesterone receptors (both, P<0.0001) [26].
• A chimeric gene consisting of 6.7 kb of the 5'-flanking region of the human NGFR gene linked to the chloramphenicol acetyltransferase gene was constructed [27].
• For 28 sets of serial examinations, NGFR was also measured by the plasma disappearance of 99mTc DTPA (measured) [28].

Physical interactions of NGFR

• The number of high-affinity NGF binding sites was nearly the same for LAN5 and LAN5/NGFR, a finding suggesting that there is a limiting number of some separately coded factor or subunit that is required for high-affinity NGFRs [18].
• Results obtained with cells transfected with the low-affinity NGF receptor gene indicate that these cells bind BDNF, in addition to NGF, whereas cells before transfection do not [29].
• The high-affinity NGF receptor is thought to be a complex of two receptors , gp75 and the tyrosine kinase TrkA, but direct biochemical evidence for such an association had been lacking [30].

Co-localisations of NGFR

• Virtually all (greater than 90%) NGF receptor-containing neurons co-localize with the specific cholinergic marker choline acetyltransferase (ChAT) within the nucleus basalis in PD [31].

Regulatory relationships of NGFR

• As determined by transient expression, two NGF response elements (REs) were required for transcription induced by NGF in SH-SY5Y cells with stable expression of an exogenous NGF receptor TRK-A gene (SH-SY5Y/trk) [32].
• The immunoreactivity for NGFR was scarcely present in the sham-control CA1 area but was induced from 1 h and markedly expressed at 7 days after recirculation in the vehicle group [33].
• The objective of the present report was to study the expression of the low affinity nerve growth factor (NGF) receptor p75 and of the activated high-affinity NGF receptor TrkA in malignant mesothelioma (MM) [34].
• We further identified the telomerase-negative subpopulation which contained a small subset that strongly coexpresses p75NGFR low affinity nerve growth factor receptor, integrin beta4 and bcl-2 protein [35].
• Most of the NGF receptor-bearing cells differed from myoid cells of the lamina propria expressing desmin, a marker for smooth muscle [36].

Other interactions of NGFR

• We document the presence of RNA message for the low- (LNGFR) and the high-affinity NGF receptor (NTRK1) by using RT-PCR on fresh BM aspirate and on LTBMC [37].
• The results demonstrate that, in addition to Grb2, CRK participates in signaling from the NGF receptor and that two GNRPs appear to transmit signals from these adaptor molecules to Ras [38].
• Furthermore, colocalization studies show that many BDNF-expressing sensory neurons also express trk A, the high-affinity NGF receptor [39].
• The low-affinity NGFR has been shown to have structural homology with another specific B cell surface molecule, CD40, which plays an important role in IgE production [40].
• No differences in the number of NGF-R mRNA-positive neurons between normal aged and AD patients were detected within the NGF-responsive cell groups of the medial septum (Ch1) and nucleus of the vertical limb of the diagonal band (Ch2) [4].

Analytical, diagnostic and therapeutic context of NGFR

• METHODS: CD34+CK7/8+ cells from midgestation livers were analyzed for the expression of various markers by flow cytometry and isolated based on their expression of CD34, nerve growth factor receptor (NGFR) and lack of CD45 expression [41].
• Immunofluorescence studies here showed that NGFR are also present on a proportion of human peripheral blood mononuclear cells (PBMC) [42].
• Northern blot and ligand binding/immunoprecipitation assays revealed four receptor-positive cell lines (NGP, NLF, SK-N-SH, and LA-N-6), with NGFR mRNA and protein of expected sizes (3.8 kilobases and Mr approximately 75,000, respectively) [43].
• Southern blot analysis showed that all 10 cell lines possess apparently normal NGFR genes [43].
• We report here on the demonstration of NGFR-like proteins from PC12 and SY5Y cells by sequential lectin chromatography, reverse-phase HPLC, and SDS-PAGE analysis of immunoprecipitates obtained with NGFR-specific monoclonal antibodies [25].

References