Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Receptor, Nerve Growth Factor”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1985

Characteristics of the nerve growth factor receptors and a nerve growth factor receptor--nerve growth factor covalent complex.

Nerve growth factor is a polypeptide hormone that is required for the normal growth and development of the embryonic sensory and sympathetic nervous systems. On these cells, there are two different receptors for the nerve growth factor. Recently, these receptors have been isolated from three cell types and shown to have essentially the same binding characteristics. Molecular weights for receptors from two of these cell types, embryonic sensory and rat pheochromocytoma cells, have been determined. In addition, the formation of a covalent nerve growth factor, nerve growth factor receptor complex, has been investigated on embryonic sensory and sympathetic neurons. The formation of this covalent complex containing 125I-beta nerve growth factor is prevented by the addition of excess unlabeled nerve growth factor or by the addition of sodium fluoride and dinitrophenol. This complex forms at 4 degrees, 22 degrees, and 37 degrees, indicating that it is occurring on the cell surface. A disulfide bond is involved in the formation of this covalent complex.

Animals↗
PubMed1991

Dependence of kidney morphogenesis on the expression of nerve growth factor receptor.

Nerve growth factor receptor (NGFR) serves as the binding site for the neurotrophic growth factors. Although NGFR has been found in several embryonic tissues outside the nervous system, the function of NGFR in embryogenesis of non-neuronal organs remains unknown. NGFR is transiently synthesized by embryonic rat kidney and disappears from nephrons upon their terminal differentiation. Anti-sense oligonucleotide inhibition of NGFR expression inhibits kidney morphogenesis. Therefore, NGFR is required not only for development of the nervous system, but also for differentiation of the kidney tubules.

Animals↗
PubMed1991

Molecular investigations on the high-affinity nerve growth factor receptor.

Nerve growth factor (NGF) receptors have been investigated by means of affinity labeling with 125I-NGF and chemical cross-linking. Two distinct NGF-receptor complexes are detected on PC12 cells; these correspond to 100 kd and 158 kd for the low-affinity (LNGFR) and the high-affinity (HNGFR) receptors, respectively. Interestingly, three different antibodies directed against distinct epitopes on the LNGFR immunoprecipitate the low-but not the high-affinity NGF-receptor complex. Although the identities of the signaling molecules in the HNGFR are unknown, antibodies to the src, ras, raf-1, and yes products fail to immunoprecipitate either receptor complex, suggesting that these molecules are not a part of, or tightly coupled to, either receptor type. Phosphotyrosine residues are found exclusively on the HNGFR complex, suggesting that tyrosine phosphorylation may be one of the initiating events in the NGF-induced signal transduction cascade.

Adrenal Gland Neoplasms↗
PubMed1991

Glycosyl-phosphatidylinositol/inositol phosphoglycan: a signaling system for the low-affinity nerve growth factor receptor.

Nerve growth factor (NGF) exerts a variety of actions during embryonic development. At the early stages of inner ear development, NGF stimulates cell proliferation, an effect mediated through low-affinity receptors. We have studied the possibility that the glycosyl-phosphatidylinositol/inositol phosphoglycan (glycosyl-PtdIns/IPG) system is involved in transmitting this NGF signal. Endogenous glycosyl-PtdIns was characterized in extracts of cochleovestibular ganglia (CVGs) that incorporated [3H]glucosamine, [3H]galactose, [3H]myristic acid, and [3H]palmitic acid. Incubation of CVG with NGF produced a rapid and transient hydrolysis of glycosyl-PtdIns. Hydrolysis was complete at 100 ng/ml, and the half-maximal effect occurred at 25 ng/ml, overlapping with the concentration dependence of the mitogenic effect of NGF. An IPG was isolated from embryonic extracts. It had biological effects similar to those reported for the insulin-induced IPG in other tissues. It exerted a powerful mitogenic effect on CVG, comparable to that of NGF. Both the IPG- and NGF-induced cell proliferation were blocked by anti-IPG antibodies that recognized the endogenous IPG on a silica plate immunoassay. These results show that CVG possesses a fully active glycosyl-PtdIns/IPG signal transduction system and that the proliferative effects associated with NGF binding to low-affinity receptors require IPG generation.

Animals↗
PubMed2000

Association of the Abl tyrosine kinase with the Trk nerve growth factor receptor.

Nerve growth factor (NGF) initiates the majority of its biological effects by promoting the dimerization and activation of the tyrosine kinase receptor TrkA. In addition to rapid increases in the phosphorylation of phosphatidylinositol 3'-kinase (PI 3-kinase) and phospholipase C-gamma and increased ras activity, phosphorylation of c-Crk and paxillin proteins has been observed upon TrkA activation. The c-Abl tyrosine kinase is involved in the control of the axonal cytoskeleton and is known to interact with c-Crk proteins. Here we have tested the possibility that TrkA receptors might form an association with the c-Abl protein. After transfection in 293T cells, TrkA and c-Abl kinases could be coimmunoprecipitated. This interaction did not require TrkA receptors to be autophosphorylated. Mapping analysis indicated that the region of c-Abl association was confined to the juxtamembrane region of TrkA. The interaction of c-Abl with TrkA was also observed in differentiated pheochromocytoma PC12 cells. These results suggest that c-Abl may be recruited to the NGF receptor complex and be involved in regulating specific phosphorylation events that occur during neuronal differentiation.

Animals↗
PubMed1997

Both p140(trk) and p75(NGFR) nerve growth factor receptors mediate nerve growth factor-stimulated calcium uptake.

Human p140(trk) and p75(NGFR) were transfected separately into 3T3 cells. Nerve growth factor stimulates calcium uptake into both transfectants but not into untransfected 3T3 cells. p140(trk) cells were stimulated maximally by 25 ng/ml; 100 ng/ml was submaximal for p75(NGFR) cells. K-252a inhibits the effect of NGF on p140(trk) cells but not on p75(NGFR) cells; brain-derived neurotrophic factor stimulates calcium uptake in p75(NGFR) cells but not in p140(trk) cells. The data suggest that both nerve growth factor receptors could be involved in the nerve growth factor-mediated actions of calcium on its target cells: neuronal survival, neuronal protection, and synaptic plasticity.

3T3 Cells↗
PubMed1997

Ethanol reduces expression of the nerve growth factor receptor, but not nerve growth factor protein levels in the neonatal rat cerebellum.

The cerebellum is especially vulnerable to ethanol's neurotoxic effects during development, and ethanol exposure during the brain growth spurt will deplete cerebellar neurons. The mechanisms undertying this neuronal cell loss remain elusive. Nerve growth factor (NGF) is a neurotrophin that promotes cell survival in various brain areas, and there is evidence that NGF may play a role in the developing cerebellum. This study examined whether ethanol exposure of the neonatal rat cerebellum altered the levels of either NGF or the expression of p75 and trkA, which are two components of the NGF receptor. Ethanol exposure had no effect on NGF levels in the neonatal cerebellum, as determined by an NGF-specific ELISA. Immunohistochemical labeling techniques indicated that both the p75 and trkA NGF receptors were expressed on Purkinje cell dendrites in the developing cerebellum, with posterior lobules expressing higher levels of p75 and trkA NGF receptor, compared with anterior lobules. Ethanol exposure of neonatal rats reduced the expression of both p75 and trkA NGF receptors on the Purkinje cell dendrites. These results suggest that ethanol could interfere with neurotrophic support of Purkinje cells by reducing the levels of available NGF receptor.

Animals↗
PubMed1987

Purification and amino terminal sequencing of human melanoma nerve growth factor receptor.

The nerve growth factor (NGF) receptor, solubilized with Triton X-100 detergent, has been purified from human melanoma cell line A875. Purification to near-homogeneity was achieved by chromatography on wheat germ agglutinin-agarose, followed by immunoaffinity chromatography on Sepharose columns coupled with anti-NGF receptor monoclonal antibody (MAb). The purified receptor, a 75,000-dalton protein, retains the capacity to bind NGF as well as anti-receptor MAbs. Final purification was achieved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The sequence of amino acid residues at the amino terminus has been determined. Possible sequence homology between the NGF receptor and several other proteins is discussed. Using the purified receptor as immunogen, new MAbs to the NGF receptor have been produced. The NGF receptor was visualized by immunoperoxidase staining in tissue sections of dorsal root ganglia from monkeys.

Amino Acid Sequence↗
PubMed1992

Retinoic acid regulates both expression of the nerve growth factor receptor and sensitivity to nerve growth factor.

In PC12 cells, retinoic acid (RA) stimulates the expression of p75NGFR, a component of the nerve growth factor (NGF) receptor, as indicated by a rapid increase in p75NGFR mRNA, an increase in the binding of 125I-labeled NGF to p75NGFR, and an increase in the binding of NGF to low affinity sites. RA-treated cells are more sensitive to NGF, but not to either fibroblast growth factor or phorbol 12-myristate 13-acetate, showing that RA has a specific effect on the responsiveness of PC12 cells to NGF. Exposure to RA leads neither to an increase in the expression of mRNA for trk, another component of the NGF receptor, nor to an increase in binding to high affinity receptors, suggesting that an increase in the expression of p75NGFR is sufficient to make cells more sensitive to NGF. This work suggests that, in addition to having direct effects on gene expression, RA can indirectly modulate differentiation of neurons by modifying their expression of cell surface receptors to peptide growth factors.

Animals↗
PubMed2005

The small GTPase Rab7 controls the endosomal trafficking and neuritogenic signaling of the nerve growth factor receptor TrkA.

Nerve growth factor (NGF) and its TrkA receptor exert important bioactivities on neuronal cells such as promoting survival and neurite outgrowth. Activated TrkA receptors are not only localized on the cell surface but also in signaling endosomes, and internalized TrkA receptors are important for the mediation of neurite outgrowth. The regulation of the endosomal trafficking of TrkA is so far unknown. Because the endosome-associated GTPase Rab7 coimmunoprecipitated with TrkA, we examined whether the endosomal trafficking of TrkA might be under the control of Rab7. Inhibiting Rab7 by expression of a green fluorescent protein-tagged, dominant-negative Rab7 variant resulted in endosomal accumulation of TrkA and pronounced enhancement of TrkA signaling in response to limited stimulations with NGF, such as increased activation of Erk1/2 (extracellular signal-regulated kinase 1/2), neurite outgrowth, and expression of GAP-43 (growth-associated protein 43). Our studies show that the endosomal GTPase Rab7 controls the endosomal trafficking and neurite outgrowth signaling of TrkA. Because mutations of Rab7 are found in patients suffering from hereditary polyneuropathies, dysfunction of Rab7 might contribute to neurodegenerative conditions by affecting the trafficking of neurotrophins. Moreover, strategies aimed at controlling Rab7 activity might be useful for the treatment of neurodegenerative diseases.

Animals↗
PubMed1987

Targeting of liposomes to cells bearing nerve growth factor receptors mediated by biotinylated nerve growth factor.

We have used biologically active derivatives of beta-nerve growth factor (NGF), modified by biotinylation via carboxyl groups, to target the specific binding of liposomes to cultured rat and human tumor cells bearing NGF receptors. Liposomes, to be used for targeting, were prepared by conjugating streptavidin to phospholipid amino groups on liposomes prepared by reverse-phase evaporation. Approximately 2,000 streptavidin molecules were incorporated per liposome. Addition of biotinylated NGF, but not of unmodified NGF, could mediate the subsequent binding of radiolabeled streptavidin-liposomes to rat pheochromocytoma PC12 cells in suspension at 4 degrees C. In contrast, incubation with biotinylated NGF did not mediate the binding of hemoglobin-conjugated liposomes. Under optimal incubation conditions, approximately 570 streptavidin-liposomes were specifically bound per cell. Biotinylated NGF was also used to obtain specific binding of streptavidin-liposomes containing encapsulated fluorescein isothiocyanate-labeled dextran to PC12 cells or human melanoma HS294 cells. When HS294 cells were incubated at 37 degrees C following targeted liposome binding at 4 degrees C, the cell-associated fluorescence appeared to become internalized, displaying a perinuclear pattern of fluorescence similar to that observed when lysosomes were stained with acridine orange. Trypsin treatment abolished cell-associated fluorescence when cells were held at 4 degrees C but did not alter the fluorescence pattern in cells following incubation at 37 degrees C. When liposomes containing carboxyfluorescein, a dye capable of diffusing out of acidic compartments, were targeted to HS294 cells, subsequent incubation at 37 degrees C resulted in diffuse cytoplasmic fluorescence, suggesting that internalized liposomes encounter lysosomal or prelysosomal organelles.

Adrenal Gland Neoplasms↗
PubMed1991

Regulation of nerve growth factor receptor gene expression by nerve growth factor in the developing peripheral nervous system.

Nerve growth factor (NGF) is a target-derived neurotrophic protein that promotes the survival and growth of developing sympathetic and sensory neurons. We have examined NGF receptor gene expression in these neurons after NGF administration. Northern blot and in situ hybridization analyses demonstrated that NGF given systemically to neonatal rats increased levels of NGF receptor mRNA in sympathetic neurons within the superior cervical ganglion. This increase was accompanied by a differential regulation of genes associated with neurotransmitter phenotype; tyrosine hydroxylase mRNA was increased, but neuropeptide Y mRNA was not. NGF receptor mRNA levels were also increased in L4-L5 dorsal root ganglia, although this mRNA was not expressed uniformly in sensory neurons of control or NGF-treated animals. Levels of T alpha 1 alpha-tubulin mRNA, a marker of neuronal growth, also increased. In contrast to developing neurons, systemic NGF did not increase NGF receptor mRNA in nonneuronal cells of the sciatic nerve. To determine if NGF regulated NGF receptor gene expression at the transcriptional level, we examined PC12 cells. NGF treatment for 6 h increased NGF receptor mRNA fourfold; this increase was inhibited by cycloheximide. Nuclear run-off transcription assays demonstrated that the increase in steady-state NGF receptor mRNA levels was mediated at the transcriptional level. In contrast, although NGF treatment increased steady-state tyrosine hydroxylase mRNA levels, this effect was not blocked by cycloheximide, and was not due to increased transcription. These data raise the possibility that transcriptional regulation of NGF receptor gene expression by target-derived NGF could be a molecular mechanism for potentiating NGF's effects on neurons during developmental periods of neuronal competition and cell death.

Adrenergic Fibers↗
PubMed1994

Frequent expression of 75 kDa nerve growth factor receptor and phosphotyrosine in human peripheral nerve tumours: an immunohistochemical study on paraffin-embedded tissues.

One hundred and three benign, and 10 malignant peripheral nerve tumours were examined immunohistochemically for expression of 75 kDa nerve growth factor receptor (NGFR). In benign tumours NGFR was demonstrated at 61% in neurinoma, 71% in neurofibroma, 93% in neurofibromatosis and 90% in traumatic neuroma. Malignant neurogenic tumours were 100% positive for NGFR. Phosphotyrosine-immunoreactivity was detected in 76% of NGFR-positive tumours but the frequency of immunostained tumour cells was low. These results suggest that both benign and malignant peripheral nerve tumours express 75 kDa NGFR. The receptor seems to serve as growth signal transduction of the tumour cells in terms of phosphorylation of the tyrosine residue of the receptor or the target protein of the NGFR protein tyrosine kinase.

Humans↗
PubMed1996

Reducing p75 nerve growth factor receptor levels using antisense oligonucleotides prevents the loss of axotomized sensory neurons in the dorsal root ganglia of newborn rats.

The low-affinity p75 receptor for nerve growth factor (p75NGFR) has been implicated in mediating neuronal cell death in vitro. A recent in vitro study from our laboratory showed that the death of sensory neurons can be prevented by reducing the levels of p75NGFR with antisense oligonucleotides. To determine if p75NGFR also functions as a death signal in vivo, we have attempted to reduce its expression in peripheral sensory neurons by applying antisense oligonucleotides to the proximal end of the transected sciatic or median and ulnar nerves. We report here that antisense oligonucleotides, when applied to the proximal stump of a transected peripheral nerve, are retrogradely transported and effectively reduce p75NGFR protein levels in sensory neurons located in the dorsal root ganglia. Furthermore, treatment of the proximal nerve stump with antisense p75NGFR oligonucleotides significantly reduced the loss of these axotomized sensory neurons. These findings further support the view that p75NGFR is a death signaling molecule and that it signals death in axotomized neurons in the neonatal sensory nervous system.

Animals↗
PubMed1996

Tissue Localization of Nerve Growth Factor Receptors: trk A and Low-Affinity Nerve Growth Factor Receptor in Neuroblastoma, Pheochromocytoma, and Retinoblastoma.

The immunohistochemical localization of nerve growth factor receptor (NGFR)-high-affinity NGFR (trk A) and low-affinity NGFR (LNGFR)-was investigated in 23 neuroblastoma group tumors, 18 pheochromocytomas, 2 mixed neuroendocrine-neural tumors, and 16 retinoblastomas. trk A was expressed in the tumor cells of all neuroblastomas, pheochromocytomas, and retinoblastomas. Immunoreactive intensity was especially strong in the larger ganglionic tumor cells of ganglioneuroblastoma and ganglioneuroma. Messenger RNA (mRNA) of trk A was also strongly expressed in the ganglionic cells of ganglioneuroblastomas and chromaffin cells of pheochromocytomas by in situ hybridization method. LNGFR was negative in the tumor cells of neuroblastoma; however, it showed strong immunoreactivity in ganglionic tumor cells and Schwann cells of ganglioneuroblastoma/ganglioneuroma, and sustentacular cells of pheochromocytoma. Although normal retina expressed both trk A and LNG FR, tumor cells of retinoblastoma were positive for only trk A but negative for LNGFR. Such differences in the expression of trk A and LNGFR may reflect neuronglial interactions in the survival and maturation of the sympathetic nerves, retina, and tumors in these tissues.

Journal Article↗
PubMed1987

Neural crest-derived proprioceptive neurons express nerve growth factor receptors but are not supported by nerve growth factor in culture.

The neural crest-derived, first-order, sensory neurons of the embryonic chick trigeminal mesencephalic nucleus were grown in dissociated, glia-free culture. Whereas brain-derived neurotrophic factor promoted the survival and growth of the majority of these neurons (over 70% after 48 h incubation), nerve growth factor had no effect on their survival. The percentage survival in cultures supplemented with nerve growth factor at concentrations ranging from 0.2 to 625 ng/ml was only 2%, the same percentage survival as in control cultures. Furthermore, nerve growth factor did not change the dose-response of these neurons to brain-derived neurotrophic factor. Although nerve growth factor did not influence the survival of trigeminal mesencephalic neurons in culture, nerve growth factor specifically bound to the great majority of neurons growing in the presence of brain-derived neurotrophic factor. Autoradiographs of cultures incubated with iodinated nerve growth factor showed that the perikarya and processes of neurons were heavily labelled with silver grains. These findings demonstrate the existence of a population of neural crest-derived sensory neurons which express nerve growth factor receptors but are not supported by nerve growth factor in culture.

Animals↗
PubMed1998

Light and electron microscopic demonstration of the p75 nerve growth factor receptor in normal human cutaneous nerve fibers: new vistas.

The nerve growth factor and its receptor are important in nerve growth, differentiation, maturation, and maintenance. In order to explore the exact distribution of p75 low-affinity nerve growth factor receptor (p75 NGFr) expression in cutaneous nerve fibers, p75 NGFr and neuron-specific enolase double immunofluorescence and immunoelectron microscopic studies were conducted on normal human skin samples. After p75 NGFr and neuron-specific enolase immunofluorescence double staining, the dermal nerves were strongly p75 NGFr-immunoreactive (IR); however, very few p75 NGFr-IR nerve fibers were found in the epidermis. p75 NGFr immunoreactivity was found mainly in the peripheral part of cutaneous nerve trunks and fibers, whereas neuron-specific enolase immunoreactivity was mainly seen within the axons. After ultrastructural immunostaining, the Schwann cell membrane was strongly p75 NGFr-IR. The Schwann cell membrane facing the connective tissue was more strongly p75 NGFr-IR than the part of the membrane close to the axon; the Schwann cell cytoplasm nearest to the membrane sometimes also showed a high p75 NGFr immunoreactivity, whereas the rest of the cytoplasm was generally more weakly p75 NGFr-IR; however, the axon itself seldom showed any such immunoreactivity; actually, only a few parts of the axonal membrane revealed a weak staining, leaving most of the membrane unstained. The axoplasm was not p75 NGFr-IR. The results--that in human cutaneous nerves it is mainly the Schwann cells that express p75 NGFr immunoreactivity--further stress the active role of the glial ensheathment in the control and maintenance of a normal target innervation.

Fluorescent Antibody Technique↗
PubMed2002

Oxidative stress modulates tyrosine kinase receptor A and p75 receptor (low-affinity nerve growth factor receptor) expression in SHSY5Y neuroblastoma cells.

The interaction of neurotrophins and their tyrosine kinase receptors (trks) is essential for differentiation and survival of brain cells. In Alzheimer's disease (AD), the number of neurotrophins and receptors is markedly decreased. The cause of this reduction is unclear, but the role of beta-amyloid (Abeta) seems central in understanding the mechanisms controlling neurotrophin and trk expression. In the study reported here, we exposed SHSY5Y neuroblastoma cells to Abeta or hydrogen peroxide (H(2)O(2)) and measured the expression of trk-A and p75 at the protein and molecular levels. Both Abeta and H(2)O(2) induced oxidative stress (measured by a decrease in cellular glutathione), which decreased trk-A levels and increased p75 levels, decreased messenger RNA (mRNA) levels of both receptors, and increased nerve growth factor (NGF) secretion. Pretreatment of cells with the antioxidant melatonin returned levels of protein expression, mRNA, and NGF secretion to normal. These results are significant, as they can help in the planning and implementation of AD treatment strategies involving neurotrophins.

Amyloid beta-Peptides↗