Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A recurrent, reciprocal balanced translocation, t(2;5) (p23;q35), has been recognized in CD30+ anaplastic large-cell lymphomas (ALCL), a newly recognized subtype comprising approximately 5% of all non-Hodgkin's lymphoma (NHL). This translocation creates a novel fusion protein, NPM-ALK, which has transforming properties in vitro and can cause large-cell lymphoma in vivo when transfected into murine bone marrow. Multiple techniques including reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of NPM-ALK fusion transcripts, genomic DNA-PCR, RNA in situ hybridization, and fluorescence in situ hybridization (FISH) of metaphase chromosomes and interphase nuclei, and immunohistochemical detection of the 80 kilodalton protein (p80) derived from the NPM-ALK fusion have enabled surveys of normal and lymphoma tissues for evidence of the translocation. These studies suggest that expression of ALK protein, a novel orphan receptor tyrosine kinase, is normally confined to the nervous system. In lymphoma, NPM-ALK expression is most often seen in young patients with the monomorphic or small-cell variant of ALCL who present with advanced stage disease and have tumors with a CD30+, T- or null-cell phenotype. It is less frequently detected in older patients and in ALCL of pleomorphic histology. In addition, expression of NPM-ALK has been found in occasional CD30 negative B-cell lymphomas with diffuse large cell or immunoblastic histology. NPM-ALK is rarely, if ever, detected in Hodgkin's disease or secondary ALCL. Although initially found in primary nodal ALCL, recent studies suggest that NPM-ALK expression may occur in lymphoma at extranodal sites, including the skin; it remains controversial, however, whether CD30+ primary cutaneous lymphoma and its benign counterpart, lymphomatoid papulosis (LyP), express NPM-ALK in some cases. A retrospective study has suggested that expression of NPM-ALK is associated with a better overall 5-year survival; these results must be confirmed in prospective studies of patients with uniform staging and therapy to more fully understand the clinical significance of the t(2;5) and its novel chimeric protein, NPM-ALK.
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PMID:The t(2;5) in human lymphomas. 968 23

The products of the human Arg gene and human, mouse, Drosophila, and nematode Abl genes characterize the Abelson family of nonreceptor tyrosine protein kinase. The Arg gene, expressed as a 12-kb transcript, codes a protein highly related to c-abl in the tyrosine kinase, SH2, and SH3 domains, and both proteins have a myristoylated isoform. The C-terminal domains of Arg and c-abl, poorly similar to each other, may account for their different functions. Arg is cytoplasmic, c-abl also has nuclear localization, and their products have different transforming activity. To gain insight about the role of Arg in myeloid differentiation we investigated Arg gene expression in HL-60 cells differentiated with all-trans retinoic acid and 12-O-tetradecanoyl-phorbol-13-acetate. With a semiquantitative reverse transcriptase-polymerase chain reaction assay it was evident that the Arg transcript level in HL-60 cells differentiated toward granulocyte and macrophage-like lineage was, respectively, 3.5- and 2.8-fold the Arg level evidenced in undifferentiated HL-60 cells. In the HL-60 cells, under the same differentiating conditions, the c-abl RNA level did not change significantly, showing that Arg and c-abl responded in a different way to the inducers of differentiation used.
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PMID:Increment of nonreceptor tyrosine kinase Arg RNA as evaluated by semiquantitative RT-PCR in granulocyte and macrophage-like differentiation of HL-60 cells. 982 10

The erbB-4 gene encodes a detected receptor protein that possesses intrinsic tyrosine kinase activity and belongs to the family of the epidermal growth factor receptor (EGFR); erbB-4 is stimulated by the heregulins and betacellulin, which enables this receptor to form heterodimers with erbB-2, a prerequisite for erbB-2 activation. Because the expression of erbB-4 mRNA is generally low in the pancreas, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the erbB-4 levels in human normal and cancerous pancreatic tissue. Our results show that the mRNA expression of this receptor is 6-fold decreased in the non-metastatic stages of pancreatic cancer when compared to tumors with lymph node or distant metastases or to the normal pancreas. In addition, immunohistochemistry demonstrated that in the normal pancreas, the erbB-4 antigen was predominantly present in the cell membrane and cytoplasm of the ductal and acinar cells and at a much lower level, in islet cells. In pancreatic cancer, 61 of 75 samples exhibited weak to moderate immunoreactivity for erbB-4 in the tumor cells. Moreover, in the peri-tumorous region with chronic pancreatitis-like morphological changes, there was weak-to-moderate erbB-4 immunostaining in small ductules and degenerating acinar cells. Uni- and multivariate survival analyses using as variables age, sex, stage of cancer, histo-pathological grading, and erbB-4 immunoreactivity, revealed a significant effect for stage of cancer (p < 0.01) whereby the risk of dying was 2.3 times higher in patients with metastases than in patients without. However, the level of erbB-4 immunoreactivity in pancreatic cancer cells had no influence on patient survival.
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PMID:ErbB-4 mRNA expression is decreased in non-metastatic pancreatic cancer. 998 27

Bovine retinal pigmented epithelial cells express an inducible nitric oxide synthase (NOS-2) after activation with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). Experiments were performed to investigate the involvement of interferon regulatory factor-1 (IRF-1) on NOS-2 induction and its regulation by NOS-2 inhibitors such as pyrrolidine dithiocarbamate (PDTC), an antioxidant, or protein kinase inhibitors. Analysis by transitory transfections showed that LPS, alone or with IFN-gamma, stimulated activity of the murine NOS-2 promoter fragment linked upstream of luciferase and its suppression by PDTC and by the different protein kinase inhibitors, genistein (tyrosine kinase inhibitor), PD98059 (mitogen-actived protein (MAP) kinase kinase inhibitor), and SB 203580 (p38 MAP inhibitor). Using specific antibodies, we have confirmed that extracellular signal-regulated kinases and p38 MAP kinase were activated by LPS and IFN-gamma in retinal pigmented epithelial cells. Analysis by reverse transcriptase-polymerase chain reaction, Western blot, and electrophoretic mobility shift assay demonstrated that IFN-gamma alone or combined with LPS induced an accumulation of IRF-1 mRNA and protein and IRF-1 DNA binding. Transfections assays with the IRF-1 promoter showed an induction of this promoter with IFN-gamma, potentiated by LPS. The decrease of LPS/IFN-gamma-induced IRF-1 promoter activity, IRF-1 synthesis, and IRF-1 activation, by PDTC, genistein, PD98059, and SB 203580, could explained in part the inhibition of the NOS-2 induction by these compounds. Our results demonstrate that IRF-1 is necessary for NOS-2 induction by LPS and IFN-gamma and that its synthesis requires the involvement of a redox-sensitive step, the activation of tyrosine kinases, and extracellular signal-regulated kinases 1/2 and p38 MAP kinases.
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PMID:Role of interferon regulatory factor-1 and mitogen-activated protein kinase pathways in the induction of nitric oxide synthase-2 in retinal pigmented epithelial cells. 998 18

Prior studies have shown that synthetic peptides representing the domain of thrombin responsible for high-affinity binding to fibroblasts stimulate chemotactic and cell proliferative signals through a nonproteolytic mechanism. One of these peptides, TP508, has recently been shown to be chemotactic for neutrophils, to enhance collagen accumulation in wounds, to enhance revascularization of wounds, and to accelerate the healing of incisional and open wounds in normal animals and in animals with impaired healing. To determine whether TP508 activates the proteolytically activated receptor for thrombin (PAR1), or the signals that are activated by PAR1, we treated human fibroblasts with TP508 and the PAR1-activating peptide, SFLLRNP, and analyzed the effects of these peptides on gene expression using differential display reverse transcriptase polymerase chain reaction. TP508 induces expression of a number of specific message fragments with short tyrosine kinase-like domains that are not induced by SFLLRNP. Sequencing full-length clones prepared by Marathon extension of TP508-induced fragments revealed that among the induced transcripts, there was a sequence with 88% homology to human annexin V. Northern analysis with authentic annexin V cDNA confirms that TP508, but not SFLLRNP, induces expression of annexin V in human fibroblasts. These results demonstrate that TP508 activates a cellular response separate from that activated through PAR1 and supports the hypothesis that TP508 acts through a separate nonproteolytically activated thrombin receptor that may be responsible for high-affinity thrombin binding and for nonproteolytic signals that are required for thrombin stimulation of cell proliferation.
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PMID:Thrombin peptide, TP508, induces differential gene expression in fibroblasts through a nonproteolytic activation pathway. 1006 70

HTK (hepatoma transmembrane kinase) is a receptor tyrosine kinase belonging to the EPH subfamily of tyrosine kinases. Binding of its ligand (HTKL) results in tyrosine phosphorylation of HTK. In the present study, we analyzed the possible involvement of this ligand-receptor signalling system in hematopoiesis by examining the expression of both HTK and HTKL in a large and comprehensive panel of 70 continuous human leukemia-lymphoma cell lines. HTK and HTKL mRNA expression were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). HTK mRNA was detected in 68/70 cell lines; 58/70 cell lines were positive for HTKL mRNA expression; consequently, co-expression of both receptor and ligand was demonstrated in the majority of cell lines. Collectively, the wide-spread expression suggests a role for this ligand-receptor pair in hematopoietic development and/or function. Investigation of the details of signal transduction pathway that is activated by the HTK tyrosine kinase will help to define the exact biological function of the HTK-HTKL system.
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PMID:Expression of receptor tyrosine kinase HTK (hepatoma transmembrane kinase) and HTK ligand by human leukemia-lymphoma cell lines. 1022 18

Angiogenesis and synovial cell hyperplasia are characteristic features of rheumatoid arthritis (RA). Many growth and survival factors use receptors belonging to the tyrosine kinase family that share conserved motifs within the intracellular catalytic domains. To understand further the molecular basis of cellular hyperplasia in RA, we have used degenerate primers based on these motifs and RNA obtained from the synovium of a patient with RA to perform reverse transcriptase-polymerase chain reaction. We report detection of the receptor tyrosine kinase (RTK) Axl in RA synovium and we document the expression pattern of Axl in capillary endothelium, in vascular smooth muscle cells of arterioles and veins, and in a subset of synovial cells in RA synovial tissue. Gas6 (for growth arrest-specific gene 6), which is a ligand for Axl and is related to the coagulation factor protein S, was found in synovial fluid and tissue from patients with RA and osteoarthritis. Axl expression and function was studied in human umbilical vein endothelial cells (HUVECs). Gas6 bound to HUVECs; soluble Axl inhibited this binding. Exogenous Gas6 protected HUVECs from apoptosis in response to growth factor withdrawal and from TNFalpha-mediated cytotoxicity. These findings may reveal a new aspect of vascular physiology, which may also be relevant to formation and maintenance of the abnormal vasculature in the rheumatoid synovium.
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PMID:Expression of receptor tyrosine kinase Axl and its ligand Gas6 in rheumatoid arthritis: evidence for a novel endothelial cell survival pathway. 1023 55

Protein tyrosine kinases (PTKs) are a major class of proto-oncogenes that are involved in tumor progression. The purpose of this study was to establish a comprehensive PTK expression profile in gastric cancers, with the objective of identifying possible biomarkers for gastric cancer progression. We have designed degenerate primers according to the consensus catalytic motifs to amplify PTK molecules from gastric cancers by reverse transcriptase-PCR methods. The PTK expression profile was established by sequencing analysis of the cloned PCR products. We have identified 17 PTKs from a gastric adenocarcinoma. Two receptor PTKs, tie-1 and axl, were selected for in situ immunohistochemistry studies because of their higher expression level and their described roles in adhesion, invasion, and angiogenesis. Among the 97 gastric adenocarcinoma tissues examined, we observed positive immunohistochemical staining of tie-1 PTK in 69 and positive staining of axl kinase in 71 tissues. Statistical analysis with clinicopathological features indicates that tie-1 kinase expression is inversely correlated with patients' survival, whereas axl fails to show similar clinical significance. Our results illustrate the utility of tyrosine kinase gene family profiling in human gastric cancers and show that tie-1 tyrosine kinase may serve as a novel independent prognostic marker for gastric adenocarcinoma patients.
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PMID:tie-1 protein tyrosine kinase: a novel independent prognostic marker for gastric cancer. 1043 78

The vascular endothelial growth factor (VEGF) family is a novel regulator of endothelial cell proliferation. We assessed the mRNA expression of VEGF, VEGF type C (VEGF-C) and their receptors together with the microvessel density (VD) and microlymphatic vessel density (LVD) in pursuit of their connection and prognostic value in malignant pleural mesothelioma (MPM). We used four human MPM cell lines, 54 MPM tumours and five normal pleural tissues. Expression levels for receptors and ligands were assessed by semiquantitative reverse transcriptase polymerase chain reaction analysis. Microvessels were highlighted by immunohistochemical staining for factor VIII. The discrimination of lymphatics was performed by enzyme-histochemistry for 5'-nucleotidase after adequate inhibition of non-specific activity. The expression levels of VEGF, VEGF-C and VEGFRs were high in all MPM cell lines. The percentages of tumours with higher expression compared to the mean values of normal pleural tissues were 31.5% (17/54) for VEGF, 66.7% (36/54) for VEGF-C, 20.4% (11/54) for fms-like tyrosine kinase (flt)-1, 42.6% (23/54) for kinase insert domain-containing recepter (KDR) and 59.3% (32/54) for flt-4. Significant positive correlations were found between VEGF-C and flt-4, VEGF and KDR, VEGF and flt-1 in tumour tissues. The association between LVD and VEGF-C expression level was especially strong (P< 0.0001, r= 0.63). There were also significant correlations between LVD and flt-4, and VD and VEGF. No correlation, however, was found between LVD and nodal metastasis. VD was a negative prognostic indicator in this study. The associations between VEGFNEGF-C and vessel density suggest that these factors play an important role in angiogenesis and lymphangiogenesis in this tumour, and assessment of vascularity may be a useful prognostic indicator for MPM patients.
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PMID:VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours. 1048 12

The Ets variant gene 6 (ETV6/TEL) gene is rearranged in the majority of patients with 12p13 translocations fused to a number of different partners. We present here a case of acute myeloid leukemia M4 with eosinophilia (AML-M4Eo) positive for the CBFb/MYH11 rearrangement and carrying a t(1;12)(q25;p13) that involves the ETV6 gene at 12p13. By 3'rapid amplification of cDNA ends-polymerase chain reaction (3'RACE-PCR), a novel fusion transcript was identified between the ETV6 and the Abelson-related gene (ARG) at 1q25, resulting in a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase (PTK) domains of ARG. The reciprocal transcript ARG-ETV6 was also detected in the patient RNA by reverse transcriptase-polymerase chain reaction (RT-PCR), although at a lower expression level. The ARG gene encodes for a nonreceptor tyrosine kinase characterized by high homology with c-Abl in the TK, SH2, and SH3 domains. This is the first report on ARG involvement in a human malignancy.
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PMID:The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts. 1059 83


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