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Gordon Guroff - One of the best experts on this subject based on the ideXlab platform.
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Both p140trk and p75NGFR Nerve Growth Factor Receptors Mediate Nerve Growth Factor-stimulated Calcium Uptake
Journal of Biological Chemistry, 1997Co-Authors: Hao Jiang, Danielle St. Ulme, Alia Chabuk, Philip Lazarovici, Miriam Lavarreda, Geneva Dickens, Gordon GuroffAbstract:Abstract Human p140trk and p75NGFR were transfected separately into 3T3 cells. Nerve Growth Factor stimulates calcium uptake into both transfectants but not into untransfected 3T3 cells. p140trk cells were stimulated maximally by 25 ng/ml; 100 ng/ml was submaximal for p75NGFR cells. K-252a inhibits the effect of NGF on p140trk cells but not on p75NGFR cells; brain-derived neurotrophic Factor stimulates calcium uptake in p75NGFR cells but not in p140trk 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.
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The Nerve Growth Factor family
Growth Factors and Cytokines in Health and Disease, 1996Co-Authors: Mari Oshima, Yoko Hirata, Gordon GuroffAbstract:Abstract The neurotrophin family now contains five members. The properties of the prototype, Nerve Growth Factor, studied for more than 40 years, are well known and reasonably well-understood. The structure of Nerve Growth Factor has been solved by X-ray diffraction and its gene has been cloned. Nerve Growth Factor is readily available through the recombinant route. The mechanism by which it acts, while not completely clear, is known in outline and is the subject of detailed research interest. A robust debate is in progress over the clinical use of Nerve Growth Factor to ameliorate some of the most catastrophic and costly human diseases. This debate has been fueled by some early indications of clinical utility. Molecular techniques have accelerated the discovery and exploration of several new neurotrophins, brain-derived neurotrophic Factor and neurotrophins 3, 4/5, and 6. These molecules share substantial homology and are of the same general physical character as Nerve Growth Factor, but with complementary and sometimes overlapping target specificities. Information about the first two makes it likely that they will also share several aspects of their action mechanisms. Their clinical utility is, as yet, a matter of speculation.
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Differentiation of PC12 cells with K-ras: comparison with Nerve Growth Factor.
Journal of neuroscience research, 1991Co-Authors: D L Simpson, M. D. Tocco, O Okuda, M Brightman, Brian B Rudkin, S Doll, S Koizumi, Geneva Dickens, M Oshima, Gordon GuroffAbstract:The cell line PC12, derived from a rat pheochromocytoma, has served as a model for studies on the mechanism of action of Nerve Growth Factor, as well as for the exploration of neuronal differentiation in general. When treated with nanomolar concentrations of Nerve Growth Factor, these neoplastic chromaffin-like cells stop dividing and acquire, for all intents and purposes, the phenotype of mature sympathetic neurons. This phenotype is characterized by the extensive outGrowth of electrically excitable neurites, the ability to form functional synapses, and the acquisition of a number of biochemical markers. Treatment of PC12 cells with retroviral vectors encoding the K-ras, the N-ras, or the v-src oncogenes also produces a marked morphological differentiation very similar to that seen upon treatment with Nerve Growth Factor. Treated cells stop dividing and develop an extensive network of neurites. It has recently been shown that PC12 cells differentiated with v-src, while resembling, morphologically, those treated with Nerve Growth Factor, differ substantially in the biochemical characteristics normally associated with Nerve Growth Factor-induced differentiation. Cells infected with K-ras also develop a neurite network similar to that seen after treatment with Nerve Growth Factor. In addition, such cells develop tetanus toxin-binding sites and saxitoxin-binding sites, as do cells treated with Nerve Growth Factor. Decreases in the binding of epidermal Growth Factor and in the activity of calpain also occur and these, as well, are characteristic of Nerve Growth Factor-treated cells. But the adhesive properties of cells infected with K-ras are different than those of Nerve Growth Factor-treated cells, and the former do not show an increase in the NILE glycoprotein. Finally, K-252a, an inhibitor of the actions of Nerve Growth Factor on PC12 cells, has no effect on the neurite outGrowth produced by infection with K-ras. Thus, many of the key markers of Nerve Growth Factor-induced differentiation of PC12 cells also appear upon differentiation with K-ras, but there are, nevertheless, some crucial differences in the properties of these two sets of cells.
Italo Mocchetti - One of the best experts on this subject based on the ideXlab platform.
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Autocrine regulation of Nerve Growth Factor expression by Trk receptors.
Journal of Neurochemistry, 2004Co-Authors: Alessandra Mallei, Stuart J. Rabin, Italo MocchettiAbstract:Activation of the neurotrophin receptor Trk induces the release of neurotrophins. However, little is known about the ability of released neurotrophins to modulate their own synthesis in an autocrine manner. As a step towards understanding the role of Trk in regulating the synthesis of neurotrophins, we exposed NIH-3T3 cells expressing TrkA or TrkC receptors to their cognate ligands as well as to GM1, a ganglioside that activates TrkA and TrkC by inducing the release of neurotrophin-3. Nerve Growth Factor and neurotrophin-3 synthesis were then determined by measuring the relative levels of protein and mRNA. TrkA-expressing cells exposed to human recombinant Nerve Growth Factor exhibited higher levels of Nerve Growth Factor mRNA. Human recombinant neurotrophin-3 evoked an increase in Nerve Growth Factor mRNA in both TrkA and TrkC-expressing cells. GM1 elicited a time-dependent increase in Nerve Growth Factor protein and mRNA in NIH-3T3 cells expressing TrkA or TrkC receptor but not in wild-type cells. Surprisingly, GM1 failed to change neurotrophin-3 levels. The ability of GM1 to increase Nerve Growth Factor mRNA levels was blocked by TrkC-IgG but not by TrkB-IgG receptor body. These data suggest that released neurotrophin-3 may activate a positive autocrine loop of Nerve Growth Factor synthesis by Trk activation.
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trkA Mediates the Nerve Growth Factor-induced Intracellular Calcium Accumulation
Journal of Biological Chemistry, 1996Co-Authors: Maria A. De Bernardi, Stuart J. Rabin, Anna Maria Colangelo, Gary Brooker, Italo MocchettiAbstract:Abstract Regulation of the cytosolic free Ca concentration by Nerve Growth Factor was investigated in C6-2B glioma cells newly expressing the high affinity Nerve Growth Factor receptor trkA, using Fura-2 fluorescence ratio imaging. In these cells, Nerve Growth Factor (50 ng/ml) evoked a novel 3-fold increase in cytosolic free Ca concentration, while no measurable Ca response was observed in wild type or mock-transfected cells lacking a functional trkA receptor. K-252a, a tyrosine kinase inhibitor which prevents Nerve Growth Factor-mediated responses in C6-2B cells expressing trkA, also blocked the rise in cytosolic free Ca concentration by Nerve Growth Factor. Moreover, basic fibroblast Growth Factor, which in these cells elicits biochemical changes similar to Nerve Growth Factor, failed to affect cytosolic free Ca concentration, further supporting the specificity of Nerve Growth Factor/trkA receptor in mediating a Ca response. While insensitive to chelation of extracellular Ca, the response was abolished following depletion of Ca stores or blockade of intracellular Ca release, providing strong evidence that intracellular Ca is the main source for Nerve Growth Factor-evoked cytosolic free Ca concentration increase. Nerve Growth Factor increased the cytosolic free Ca concentration also in NIH3T3 cells overexpressing trkA but devoid of p75 Nerve Growth Factor receptor. Our data suggest that trkA but not p75 is required for Nerve Growth Factor-evoked Ca signaling.
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TrkA mediates the Nerve Growth Factor-induced intracellular calcium accumulation.
The Journal of biological chemistry, 1996Co-Authors: Maria A. De Bernardi, Anna Maria Colangelo, Gary Brooker, S J Rabins, Italo MocchettiAbstract:Regulation of the cytosolic free Ca2+ concentration by Nerve Growth Factor was investigated in C6-2B glioma cells newly expressing the high affinity Nerve Growth Factor receptor trkA, using Fura-2 fluorescence ratio imaging. In these cells, Nerve Growth Factor (50 ng/ml) evoked a novel approximately 3-fold increase in cytosolic free Ca2+ concentration, while no measurable Ca2+ response was observed in wild type or mock-transfected cells lacking a functional trkA receptor. K-252a, a tyrosine kinase inhibitor which prevents Nerve Growth Factor-mediated responses in C6-2B cells expressing trkA, also blocked the rise in cytosolic free Ca2+ concentration by Nerve Growth Factor. Moreover, basic fibroblast Growth Factor, which in these cells elicits biochemical changes similar to Nerve Growth Factor, failed to affect cytosolic free Ca2+ concentration, further supporting the specificity of Nerve Growth Factor/trkA receptor in mediating a Ca2+ response. While insensitive to chelation of extracellular Ca2+, the response was abolished following depletion of Ca2+ stores or blockade of intracellular Ca2+ release, providing strong evidence that intracellular Ca2+ is the main source for Nerve Growth Factor-evoked cytosolic free Ca2+ concentration increase. Nerve Growth Factor increased the cytosolic free Ca2+ concentration also in NIH3T3 cells overexpressing trkA but devoid of p75 Nerve Growth Factor receptor. Our data suggest that trkA but not p75 is required for Nerve Growth Factor-evoked Ca2+ signaling.
J K Brennan - One of the best experts on this subject based on the ideXlab platform.
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Marcophate colony‐stimulating Factor in Nerve Growth Factor preparations
Journal of Neuroscience Research, 2004Co-Authors: Connie L. Erickson-miller, Robert W. Stach, C. N. Frantz, Camille N Abboud, J K BrennanAbstract:: Following a report that Nerve Growth Factor preparations have granulocyte-colony-stimulating activity, we investigated the presence of colony-stimulating Factors in 7s mouse submaxillary Nerve Growth Factor and its subunits. Macrophage colonies were formed in mouse bone marrow cultures after exposure to preparations of 7s Nerve Growth Factor, the gamma subunit, and, to a small extent, the alpha subunit; the beta subunit, which is responsible for the Nerve Growth function, did not stimulate colony Growth. Furthermore, the esteropeptidase activity of the gamma subunit was not detected in preparations of macrophage colony-stimulating Factor purified from the giant cell tumor (GCT) cell line. Immunoprecipitation of radiolabeled gamma subunit with a polyclonal antibody to L-cell macrophage colony-stimulating Factor showed a protein band that could represent the gamma subunit of Nerve Growth Factor. Separation of the macrophage activity from the esteropeptidase activity of the gamma subunit was accomplished on the basis of molecular size. Thus, macrophage colony-stimulating Factor was a contaminant of Nerve Growth Factor produced by the mouse submaxillary gland and copurified with the gamma subunit.
Robert W. Stach - One of the best experts on this subject based on the ideXlab platform.
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Disulfide bond formation between Nerve Growth Factor and the Nerve Growth Factor receptor from embryonic sensory neurons
Journal of Neurochemistry, 2006Co-Authors: Gerard A. Compito, Barbara J. Wagner, Robert W. StachAbstract:: Recent studies with sympathetic neurons using radiolabeled Nerve Growth Factor have indicated that a high-molecular-weight covalent complex is formed. This complex is between the Nerve Growth Factor and the highaffinity (type I) receptor and occurs through the formation of a disulfide bond. Studies presented in the present article demonstrate a similar complex is formed on chicken embryonic sensory neurons. The formation of this complex is inhibited by the addition of unlabeled Nerve Growth Factor, metabolic energy inhibitors (dinitrophenol and NaF), and of sulfhydryl reagents. On the other hand, formation of this complex is not inhibited by temperature, or by the addition of insulin or epidermal Growth Factor. The receptor involved in the covalent complex formation is the high-affinity (type I) receptor. The molecular weight of this complex is approximately 232,000 daltons. Evidence indicates that this covalent complex may be required for the biological activity of the Nerve Growth Factor.
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Marcophate colony‐stimulating Factor in Nerve Growth Factor preparations
Journal of Neuroscience Research, 2004Co-Authors: Connie L. Erickson-miller, Robert W. Stach, C. N. Frantz, Camille N Abboud, J K BrennanAbstract:: Following a report that Nerve Growth Factor preparations have granulocyte-colony-stimulating activity, we investigated the presence of colony-stimulating Factors in 7s mouse submaxillary Nerve Growth Factor and its subunits. Macrophage colonies were formed in mouse bone marrow cultures after exposure to preparations of 7s Nerve Growth Factor, the gamma subunit, and, to a small extent, the alpha subunit; the beta subunit, which is responsible for the Nerve Growth function, did not stimulate colony Growth. Furthermore, the esteropeptidase activity of the gamma subunit was not detected in preparations of macrophage colony-stimulating Factor purified from the giant cell tumor (GCT) cell line. Immunoprecipitation of radiolabeled gamma subunit with a polyclonal antibody to L-cell macrophage colony-stimulating Factor showed a protein band that could represent the gamma subunit of Nerve Growth Factor. Separation of the macrophage activity from the esteropeptidase activity of the gamma subunit was accomplished on the basis of molecular size. Thus, macrophage colony-stimulating Factor was a contaminant of Nerve Growth Factor produced by the mouse submaxillary gland and copurified with the gamma subunit.
Connie L. Erickson-miller - One of the best experts on this subject based on the ideXlab platform.
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Marcophate colony‐stimulating Factor in Nerve Growth Factor preparations
Journal of Neuroscience Research, 2004Co-Authors: Connie L. Erickson-miller, Robert W. Stach, C. N. Frantz, Camille N Abboud, J K BrennanAbstract:: Following a report that Nerve Growth Factor preparations have granulocyte-colony-stimulating activity, we investigated the presence of colony-stimulating Factors in 7s mouse submaxillary Nerve Growth Factor and its subunits. Macrophage colonies were formed in mouse bone marrow cultures after exposure to preparations of 7s Nerve Growth Factor, the gamma subunit, and, to a small extent, the alpha subunit; the beta subunit, which is responsible for the Nerve Growth function, did not stimulate colony Growth. Furthermore, the esteropeptidase activity of the gamma subunit was not detected in preparations of macrophage colony-stimulating Factor purified from the giant cell tumor (GCT) cell line. Immunoprecipitation of radiolabeled gamma subunit with a polyclonal antibody to L-cell macrophage colony-stimulating Factor showed a protein band that could represent the gamma subunit of Nerve Growth Factor. Separation of the macrophage activity from the esteropeptidase activity of the gamma subunit was accomplished on the basis of molecular size. Thus, macrophage colony-stimulating Factor was a contaminant of Nerve Growth Factor produced by the mouse submaxillary gland and copurified with the gamma subunit.