Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to gain insight into potential roles of neurotrophins in Schwann cell biology, the expression of neurotrophin receptors of the trk gene family was investigated in rat sciatic nerve development. This analysis revealed differential regulation of truncated and full-length receptors. TrkA was undetectable even when analysed with a sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) method. TrkB was present at the mRNA as well as protein level only in its truncated form. Surprisingly, multiple isoforms of trkC, including full-length forms, were detected in early postnatal nerve. Specific antibodies detected truncated and full-length trkC proteins in Western blotting, and RT-PCR revealed the presence of two full-length isoforms, one of them containing the 14 amino acid kinase insert. In situ hybridisation localized the expression of trkC to a subpopulation of Schwann cells. TrkC receptors are expressed already in nerves from day-16 embryos. In contrast to early postnatal stages, full-length trkC receptors are no longer expressed in adult nerves, which, however, maintain expression of truncated trkC transcripts. The presence of trkC kinases in peripheral nerve suggests a role for neurotrophin-3, the only known trkC ligand, in peripheral nerve development.
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PMID:Developmental regulation of full-length trkC in the rat sciatic nerve. 761 27

The nerve growth factor (NGF) family of neurotrophins exerts effects by binding to products of the trk family of proto-oncogenes. We examined the expression of both trk and neurotrophin mRNA during the entire range of development of quail dorsal root ganglia (DRG) and sympathetic ganglia (SG) using in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR). TrkC mRNA was present in neurons or their precursors from the time of formation of DRG (stage 18, embryonic day 2.5 [E2.5]) and throughout development. The number of labeled cells changed, however, from a majority to a minority at later developmental stages. Expression of trkA mRNA was not detected in DRG until stage 30 (E6) by in situ hybridization, although results with RT-PCR were positive at stage 23 (E3.5). Labeling was always detected on a majority of neurons or their precursors. SG exhibited low levels of trkC mRNA during the later stages of development, whereas trkA mRNA was present from stage 34 onward in most neurons. We have also shown that NGF, neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF) mRNA were present at all stages examined (stages 23 through 45 for DRG, stages 35-36 and 45 for SG). In DRG, NGF mRNA expression was limited to support cells, whereas NT-3 and BDNF mRNA were detected in both neurons and support cells. These results suggest that neurotrophins could serve a local function in developing ganglia, which can be correlated with the presence of their respective receptors.
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PMID:Expression of trk and neurotrophin mRNA in dorsal root and sympathetic ganglia of the quail during development. 786 Nov 16

Nerve growth factor causes mediator release from rat peritoneal mass cells in the presence of lysophosphatidylserine. We have investigated the neurotrophin and receptor specificity involved in this response. Nerve growth factor produced a dose-dependent release of [14C]serotonin in the presence of lysophosphatidylserine with an EC50 of approximately 1 nM. Incubation with brain-derived neurotrophic factor and neurotrophin-3 did not produce a response. Northern blot analysis with probes for low affinity nerve growth factor receptor (p75), trkA, trkB, and trkC demonstrated a detectable signal for trkA only. Western blots of trkA immunoprecipitates from mast cell culture lysates, probed with anti-phosphotyrosine antibodies, demonstrated expression of functional TrkA protein. To determine whether p75, trkB, or trkC mRNA was present in amounts below the limit of detection for Northern analysis, a sensitive reverse transcriptase polymerase chain reaction protocol was used; again rat peritoneal mast cells demonstrated only trkA. The predominant form of trkA message expressed in rat peritoneal mast cells was smaller than the neuronal form. An 18-nucleotide exon (coding for 6 amino acids in the extracellular domain) in the neuronal message was not found in the predominant mast cell trkA message. PC12 cells, a rat pheochromocytoma cell line, and dissociated rat sympathetic neurons showed both trkA and p75, but not trkB or trkC. Anterior pituitary expressed both trkB and trkC, but not trkA. To confirm the lack of expression of p75 on mast cells, 125I-nerve growth factor was chemically cross-linked to mast cells or PC12 cells and then immunoprecipitated with a monoclonal antibody specific for p75, 192-IgG; no p75 was detected. Thus, mediator release from rat peritoneal mast cells by nerve growth factor was specific and not a general property of neurotrophins, and the response was modulated through the trkA proto-oncogene. To our knowledge, this is the first description of a bone marrow-derived cell type that expresses trkA at both the mRNA and protein levels. These data provide further evidence that p75 is not necessary for nerve growth factor signal transduction.
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PMID:Mediator release from mast cells by nerve growth factor. Neurotrophin specificity and receptor mediation. 832 66

Childhood neuroblastoma tumours of the sympathetic nervous system show a remarkable clinical heterogeneity ranging from spontaneous regression to unfavourable outcome despite intensive therapy. Favourable neuroblastomas often express high levels of trkA mRNA, encoding the tyrosine kinase receptor for nerve growth factor. We have investigated mRNA expression for the neurotrophin receptor trkC in 23 primary neuroblastomas using a sensitive RNAase protection assay. TrkC expression was detected in 19 of these tumours at highly variable levels with a 300-fold difference between the highest and lowest values. Significantly higher levels of trkC mRNA were found in tumours from patients with favourable features such as low age (P < 0.012), favourable tumour stage (P < 0.012) and favourable prognosis (P < 0.05). Children with intermediate or high trkC mRNA expression had better prognosis compared with those with low or undetectable levels (83.3% vs 20%, P = 0.005). Further characterisation of trkC mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR) showed that mRNA encoding the full-length cytoplasmic tyrosine kinase domain of the receptor was only expressed in a subset of favourable tumours. These data show that favourable neuroblastomas may express the full trkC receptor while advanced tumours, in particular MYCN-amplified neuroblastoma, seem to either express no trkC or truncated trkC receptors of as yet unknown biological function. These data are suggestive of a role for trkC and its preferred ligand neutotrophin-3, NT-3, in neuroblastoma differentiation and/or regression.
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PMID:Expression of mRNA for the neurotrophin receptor trkC in neuroblastomas with favourable tumour stage and good prognosis. 879 81

The neurotrophin tyrosine kinase receptors trkA, trkB, and trkC have been isolated and sequenced from several mammalian species. Their cognate ligands nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4), and neurotrophin-3 (NT-3) act as survival and trophic factors for neurons in the peripheral nervous system (PNS). In this study we have focused on the isolation and expression of the chicken trkA homologue. In addition to a near full-length cDNA sequence described, including an extracellular six amino-acid motif earlier found in neuronal TrkA in human and rat, a novel insert of 150 base pairs (bp) between subdomains IX and X in the otherwise well-conserved intracellular kinase domain is reported. Phylogenetic analysis showed the relationship between chicken trkA and the mammalian trkA receptors. Comparisons of the extracellular domains showed some amino-acid motifs of putative NGF binding function to be well conserved in chicken TrkA. The early expression of trkA mRNA, including the alternatively spliced insert form, was localized by in situ hybridization. As early as embryonal day 3 (E3), trkA mRNA is expressed in the condensing dorsal root ganglia, and at E4 distinct trkA mRNA expression appears in the primary sympathetic chain ganglia. Finally, using a reverse transcriptase-polymerase chain reaction (RT-PCR) approach, we found that among several tested growth factors only fibroblast growth factor-2 (FGF-2) upregulated trkA mRNA expression in E9 sympathetic ganglion explants. This upregulation of trkA was corroborated by subsequent NGF-stimulated fiber outgrowth.
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PMID:Molecular cloning of the chicken trkA and its expression in early peripheral ganglia. 889 7

The distinct biological effects of neurotrophins are mediated in part through their binding to the high-affinity neurotrophin receptors represented by the Trk family of receptor tyrosine kinases. Using the technique of reverse transcriptase-polymerase chain reaction (RT-PCR), we cloned several partial cDNAs encoding trkA, trkB, and trkC from fetal brains of African green monkeys. Southern analysis of PCR products showed that the ventral tegmental area of adult monkey and ventral midbrains of fetal monkeys of E59, E81, E91, and E150 days of gestation expressed all three trk gene transcripts, whereas only trkB and trkC mRNAs were detectable in the adult substantia nigra. The nucleotide sequences of the cloned monkey trk cDNAs are highly homologous to their human counterparts, and we detected a splice variant of trkC that has recently been described in humans, but not in rodents. Moreover, sequencing of trkC cDNAs derived from four fetal monkey midbrains revealed two novel variants with single nucleotide substitution. A missense mutation (AAT to AGT) was identified in the codon corresponding to codon 361 of the deduced human TrkC sequence, converting an encoded Asn to Ser. The second variant involves a silent transition at the third nucleotide of the codon Gly 362 (GGC to GGA). Furthermore, three of the four potential alleles involving these two trkC variants were detected in these monkeys, indicating that a segregation of multiple trkC alleles occurs in a geographically contained population of feral monkeys.
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PMID:Identification of novel variants of trkC mRNA transcripts in brain of African green monkeys. 900 Apr 56

We studied the expression of mRNAs of neurotrophin (NTF) receptors trkA, trkB and trkC in single rat trigeminal ganglion neurons at embryonic days 12 and 16 to determine, whether single trigeminal ganglion neurons express one trk family member or coexpress several of them. For that purpose we elaborated a sensitive technique of reverse transcriptase-polymerase chain reaction to detect all neurotrophin receptors in a single neuron. Expression of neurofilament light chain mRNA was used as a positive marker to confirm the recovery of mRNAs from single neurons. Neurofilament-positive samples were subsequently analyzed for the expression of mRNAs for catalytic trkA, trkB, and trkC, and in some cases, low-affinity neurotrophin receptor (p75). We found neurons expressing one, coexpressing two, or even all three trk receptors. In many neurons analyzed, p75 mRNA was coexpressed with trks, but we also found neurons expressing only trks without p75, and a neuron expressing p75 alone. There were also neurons containing neither trk receptors nor p75. We provide here first direct evidence that single sensory neurons can simultaneously express three or even four neurotrophin receptors.
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PMID:mRNAS for one, two or three members of trk receptor family are expressed in single rat trigeminal ganglion neurons. 903 27

Neurotrophins are known to influence Schwann cells during development and to promote peripheral nerve regeneration after axonal damage. In neoplastic conditions. Schwann cells from experimentally-induced schwannomas appear to retain their responsiveness to nerve growth factor (NGF), although the role of neurotrophins in the neoplastic process in poorly understood. In this study, human neoplastic Schwann cells (five cases of acoustic schwannoma and two cases of malignant peripheral nerve sheath tumours [MPNST]) were investigated for the expression in situ of molecules of the neurotrophin system. In particular, we studied the 75 kDa low-affinity receptor (p75) and the mRNA for its ligands, NGF and neurotrophin-3 (NT-3). By immunohistochemistry, the p75 receptor was found to be the present at high levels in Schwann cells from acoustic schwannomas, whereas it was very weak or absent in MPNST. Messenger RNA for NGF and NT-3 was detected by reverse transcriptase in situ polymerase chain reaction technique and showed the same fluctuation of p75, being up-regulated in acoustic schwannomas and very weak or absent in MPNST. In normal non-neoplastic tissue, no detectable amounts of either ligand or receptor were observed. Our results indicate that changes in the expression of neurotrophins and their p75 receptor occurred during the neoplastic transformation of Schwann cells. In benign schwannomas, such changes are likely to reflect the loss of axonal contact, while in MPNST they may be related to a complete derangement of cell machinery in the tumour cells.
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PMID:Human neoplastic Schwann cells: changes in the expression of neurotrophins and their low-affinity receptor p75. 936 63

Expression of neurotrophins in pure microglia cultured from embryonic rat brain and the effects of lipopolysaccharide (LPS) on the expression were investigated. In untreated cultures, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin (NT)-4/5 mRNAs were detected by use of reverse transcriptase-polymerase chain reaction but NT-3 mRNA was not. LPS stimulation caused a marked increase in BDNF mRNA expression in addition to a slight increment of the NT-4/5 mRNA level; however, the NGF mRNA level was not affected. LPS also increased BDNF-like immunoreactivity in cultured microglia, an action consistent with an elevation of BDNF mRNA. These results demonstrate that LPS stimulates synthesis of BDNF and probably NT-4/5, specific ligands for tyrosine kinase receptor TrkB, suggesting that activated microglia, which appear in the damaged brain, participate in neuronal regeneration via production of such neurotrophins.
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PMID:Lipopolysaccharide enhances synthesis of brain-derived neurotrophic factor in cultured rat microglia. 945 17

Early postnatal application of thyroid hormones to rats results in morphological changes in septum and hippocampus. Modulation in the expression of either neurotrophins and/or their receptors is postulated to be responsible for these effects. In the present study we tested whether thyroxine administration leads to changes in the expression of neurotrophins of the nerve growth factor (NGF) family. Newborn rats were treated daily with subcutaneous injections of thyroxine until postnatal day (P) 12 at maximum. The pups were killed at defined intervals from P2 to 21. The septal area and the hippocampi were analyzed using the reverse transcriptase-PCR method for quantitation of NGF, brain-derived neurotrophic factor (BDNF), NT-3, and NT-4 messenger RNA (mRNA) levels. In hippocampus of hyperthyroid rats, as compared to controls, we found higher levels of BDNF and NT-3 mRNA over the total investigation period, whereas in the septum a thyroxine-dependent increase in NT-3 mRNA expression was observed. In addition, significant thyroxine-induced effects were found for all variables (except for NGF in the septum) at particular postnatal days. From these data we conclude that modulation of neurotrophin expression is a possible mechanism for the morphological modifications within the hippocampal mossy fiber system and the septohippocampal cholinergic system.
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PMID:Modulation of mRNA expression of the neurotrophins of the nerve growth factor family and their receptors in the septum and hippocampus of rats after transient postnatal thyroxine treatment. I. Expression of nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin 4 mRNA. 952 30


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