Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To better understand opioid binding parameters found in situ, binding studies were conducted to mu-opioid receptors on intact SH-SY5Y neuroblastoma cells and compared with binding to SH-SY5Y membrane and guinea pig brain membrane preparations. The mu-selective peptide antagonist [3H]D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) was used for the binding studies. The fact that CTOP is an antagonist and hydrophilic is important for binding to be achieved using intact cells. In intact cells, using a physiological buffer, there appears to be only a low affinity "agonist" conformation of the receptor. This is in contrast to binding in either brain or SH-SY5Y membranes in Tris buffer, in which high-affinity agonist binding was prevalent. As expected from the binding profiles, pertussis toxin treatment of cells has no effect on binding to intact cells, but significantly decreases affinity of agonists to cell membranes. In intact cells, binding appears to be to a single site and a single state of the mu receptor. Although in membrane preparations inhibition curves are shallow, with slope factors less than 1.0 for many agonists, on intact cells agonist inhibition curves are very steep, with slope factors slightly greater than 1.0.
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PMID:Comparison of mu opioid receptor binding on intact neuroblastoma cells with guinea pig brain and neuroblastoma cell membranes. 134 68

In papillary thyroid carcinomas, we have identified two tumor-specific rearrangements of the RET proto-oncogene leading to the formation of different transforming fusion products sharing the tyrosine kinase (tk) domain of the proto-oncogene and designated ptc-1 and ptc-2. We have analysed ptc-1 and ptc-2 products by immunoprecipitation with specific anti-RET antibodies followed by immunoblotting with the same reagent or with antibodies specific for phosphotyrosine (P-tyr) residues. The anti-RET antibodies were reactive with 64-kDa (p64ptc-1) and 81-kDa (p81ptc-2) proteins from lysates of ptc-1 and ptc-2 transformed cells, respectively, and identified two proteins of 140 kDa and 160 kDa from extracts of SK-N-SH, a neuroblastoma cell line previously shown to express two differently glycosylated forms of the normal RET product. The anti P-tyr antibodies, while detecting the same p64ptc-1 and p81ptc-2 proteins from ptc-1 and ptc-2 extracts, did not show any specific band in the neuroblastoma lysates. An additional set of experiments led us to conclude that, whereas the normal product of the RET proto-oncogene is a membrane-associated receptor-like molecule not intrinsically phosphorylated on tyrosine, both oncogenic forms of RET, ptc-1 and ptc-2, are constitutively phosphorylated on tyrosine, display an 'in vitro' autophosphorylation activity, are translocated from the membrane to the cytoplasm and are apparently unaffected by protein kinase C modulation.
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PMID:Identification of the product of two oncogenic rearranged forms of the RET proto-oncogene in papillary thyroid carcinomas. 143 45

Na(+)-dependent amino isobutyric acid transport by two neuroblastoma cell lines with and without amplification of the oncogene N-myc is studied. Surprisingly, the contribution of system A is greater in the cell line showing no N-myc amplification. Preliminary data support a role for essential tyrosine and cysteine residues in the active center of the carriers, mainly in system A.
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PMID:Na(+)-dependent AIB transport by neuroblastoma cells. 145 99

Parameters of ligand binding, stimulation of low-Km GTPase, and inhibition of adenylate cyclase were determined in intact human neuroblastoma SH-SY5Y cells and in their isolated membranes, both suspended in identical physiological buffer medium. In cells, the mu-selective opioid agonist [3H]Tyr-D-Ala-Gly(Me)Phe-Gly-ol ([3H]DAMGO) bound to two populations of sites with KD values of 3.9 and 160 nM, with less than 10% of the sites in the high-affinity state. Both sites were also detected at 4 degrees C and were displaced by various opioids, including quaternary naltrexone. The opioid antagonist [3H]naltrexone bound to a single population of sites, and in cells treated with pertussis toxin the biphasic displacement of [3H]naltrexone by DAMGO became monophasic with only low-affinity binding present. The toxin specifically reduced high-affinity agonist binding but had no effect on the binding of [3H]naltrexone. In isolated membranes, both agonist and antagonist bound to a single population of receptor sites with affinities similar to that of the high-affinity binding component in cells. Addition of GTP to membranes reduced the Bmax for [3H]DAMGO by 87% and induced a linear ligand binding component; a low-affinity binding site, however, could not be saturated. Compared with results obtained with membranes suspended in Tris buffer, agonist binding, including both receptor density and affinity, in the physiological medium was attenuated. The results suggest that high-affinity opioid agonist binding represents the ligand-receptor-guanine nucleotide binding protein (G protein) complex present in cells at low density due to modulation by endogenous GTP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Opioid signal transduction in intact and fragmented SH-SY5Y neural cells. 156 Feb 22

Recent reports suggest that protein phosphorylation is involved in neural differentiation. We have found that specific inhibitors of protein phosphorylation at tyrosine residues, Erbstatin, Genistein, Herbimycin A, effectively induce neural differentiation in a human neuroblastoma cell line SK-N-DZ and a human medulloblastoma cell line Med-3, as indicated by the marked increase in the number of neurites/cell and in the expression of neurofilaments (160 k) detected by immunohistochemical studies. Possible involvement of protein phosphorylation at tyrosine residues in the differentiation of neural tumor cells was stressed.
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PMID:[Inhibitors for protein tyrosine kinases, erbstatin, genistein and herbimycin A, induce differentiation of human neural tumor cell lines]. 166 58

Notexin from Notechis scutatus scutatus snake venom was subjected to tyrosine modification with p-nitrobenzenesulphonyl fluoride (NBSF), and four modified derivatives were separated by h.p.l.c. The results of amino acid analysis and sequence determination revealed that only Tyr-7, Tyr-70 and Tyr-77 were modified in notexin. Modification of Tyr-7 resulted in decreases in lethal toxicity and enzymic activity by 70.2% and 22.7% respectively. Conversely, modification of Tyr-77 caused a 1.8-fold increase in enzymic activity, in contrast with the loss of 52.5% of lethality. A drastic decrease in lethal toxicity was observed when both Tyr-7 and Tyr-70 were modified, whereas the enzymic activity decreased by only 35.8%. Likewise, the derivative in which Tyr-7 and Tyr-77 were modified retained 44.4% of enzymic activity, but showed a marked decrease in lethal toxicity. It is obvious that modification of tyrosine residues causes a decrease in lethal toxicity of notexin, which does not directly correlate with the change in enzymic activity. On the other hand, the antigenicity of NBS derivatives remained unchanged. The modified derivatives retained their affinity for Ca2+, indicating that the modified tyrosine residues did not participate in Ca2+ binding. These results indicate that modification of tyrosine residues can differentially influence the enzymic activity and lethal toxicity of notexin, and suggest that notexin might possess two functional sites, one being responsible for the catalytic activity and the other associated with its lethal effect.
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PMID:Dissociation of lethal toxicity and enzymic activity of notexin from Notechis scutatus scutatus (Australian-tiger-snake) venom by modification of tyrosine residues. 176 38

In order to determine affinities at the mu opioid receptor binding was conducted to intact SH-SY5Y neuroblastoma cells using the mu-selective ligand [3H][H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2] [( 3H]CTOP). Binding appeared to be a single receptor site, and a single state of the mu receptor. Under intact cell conditions, some but not all mu agonists display low affinity binding, while antagonists maintain high affinity for the mu receptor. These studies indicate the usefulness of [3H]CTOP for the determination of affinities at the mu receptor under physiological conditions.
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PMID:Mu-opioid receptor binding in intact SH-SY5Y neuroblastoma cells. 196 47

The proto-oncogene product pp60c-src is a tyrosine-specific kinase with a still unresolved cellular function. High levels of pp60c-src in neurons and the existence of a neuronal pp60c-src variant, pp60c-srcN, suggest participation in the progress or maintenance of the differentiated phenotype of neurons. We have previously reported that phorbol esters, e.g., 12-O-tetradecanoylphorbol-13-acetate (TPA), stimulate human SH-SY5Y neuroblastoma cells to neuronal differentiation, as monitored by morphological, biochemical, and functional differentiation markers. In this report, we describe activation of the pp60src (pp60c-src and pp60c-srcN) kinase activity observed at 6 h after induction of SH-SY5Y cells with TPA. This phenomenon coincides in time with neurite outgrowth, formation of growth cone-like structures, and an increase of GAP43 mRNA expression, which are the earliest indications of neuronal differentiation in these cells. The highest specific src kinase activity (a three- to fourfold increase 4 days after induction) was noted in cells treated with 16 nM TPA; this concentration is optimal for development of the TPA-induced neuronal phenotype. During differentiation, there was no alteration in the 1:1 ratio of pp60c-src to pp60c-srcN found in untreated SH-SY5Y cells. V8 protease and trypsin phosphopeptide mapping of pp60src from in vivo 32P-labeled cells showed that the overall phosphorylation of pp60src was higher in differentiated than in untreated cells, mainly because of an intense serine 12 phosphorylation. Tyrosine 416 phosphorylation was not detectable in either cell type, and no change during differentiation in tyrosine 527 phosphorylation was observed.
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PMID:Early activation of endogenous pp60src kinase activity during neuronal differentiation of cultured human neuroblastoma cells. 213 66

The proto-oncogene c-src codes for two tyrosine kinases, pp60c-src and pp60c-srcN. The latter protein appears to be exclusively expressed in neurons and neuronally differentiated tumors. In cell lines derived from neuroblastoma and small-cell lung carcinoma, src expression correlates positively with neuroendocrine differentiation. However, pp60c-srcN is expressed only in highly differentiated neuroblastomas. Although c-src expression in neuroendocrine tumors probably reflects and is the result of the differentiation stage at which the tumors have been arrested, high c-src expression and kinase activities in non-neuroectodermal tumors, e.g., colon carcinoma, breast carcinoma, might instead be a part of the malignant phenotype and contribute to the development of these tumors.
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PMID:src expression in small-cell lung carcinoma and other neuroendocrine malignancies. 217 63

Cholecystokinin (CCK) receptors reside on a large number of cell types along the digestive tract and in the nervous system. A human neuroblastoma cell line (CHP212) has recently been described to express a type A receptor, with structural specificity similar to that on pancreatic acinar cells and gall bladder smooth muscle cells but different from the predominant type of binding site found in brain (type B). In this work, we have performed photoaffinity labeling and protease peptide mapping of the CHP212 receptor and have compared it to other type A CCK receptors. 125I-D-Tyr-Gly-[(Nle28,31,pNO2-Phe33)-CCK-26-33], a probe that possesses a photolabile residue at position 33 within the theoretical receptor-binding domain of this hormone, specifically labeled a Mr = 80,000-90,000 glycoprotein on this cell line, while labeling larger proteins (Mr = 85,000-95,000) on rat pancreas and human gall bladder. Deglycosylation with endo-beta-N-acetylglucosaminidase F yielded bands of Mr = 43,000 from CHP212 and gall bladder and Mr = 42,000 from pancreas. Peptide mapping of the deglycosylated bands using Staphylococcus aureus V8 protease demonstrated identical patterns in CHP212 and gall bladder and a similar but different pattern in pancreas. Thus, although possessing heterogeneity in their carbohydrate domains, CCK receptors on human neuroblastoma cells (CHP212) and human gall bladder smooth muscle cells have highly similar or identical protein cores. The core protein on another type A CCK receptor, from rat pancreas, appears to differ from these, likely representing molecular heterogeneity between species.
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PMID:Biochemical characterization of the cholecystokinin receptor on CHP212 human neuroblastoma cells. 220 Sep 53


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