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

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have analyzed the limiting factors involved in the induction of human immunodeficiency virus type 1 (HIV-1) provirus expression by tumor necrosis factor-alpha (TNF-alpha), phorbol-12-myristate-13-acetate (PMA), and bryostatin-1 in T-cells (ACH-2) and monocytes (U1). We have demonstrated that, while there is a correlation among the increase of 9.2-kilodalton (kDa) HIV-1 RNA, the increase of viral proteins (p24) in the cells, and the release of HIV-1 virions into the medium, there is no direct correlation between the levels of induced NF-kappa B binding proteins and the expression of HIV-1 provirus. The presence of nuclear NF-kappa B-specific proteins appears to be essential only for the initiation of viral replication, since the HIV-1 transcripts could be detected in TNF-alpha or bryostatin-1-stimulated cells also at later times postinduction, times when no NF-kappa B proteins could be detected in the nucleus. The uv crosslinking of DNA and proteins has shown that TNF-alpha, PMA, and bryostatin-1 induce different sets of NF-kappa B binding proteins with distinct kinetics of binding.
...
PMID:Activation of human immunodeficiency virus type 1 provirus in T-cells and macrophages is associated with induction of inducer-specific NF-kappa B binding proteins. 137 Oct 30

DNA was prepared from normal tissue and 19 lung cancer cell lines. Using probes which detect restriction fragment length polymorphisms at both the topoisomerase II alpha and beta loci, heterozygosity was detected at a frequency of 0.17 and 0.37 for the alpha and beta loci, respectively. Southern blot analysis of DNA extracted from lung cancer cell lines detected amplification of both the topoisomerase II alpha and ERBB2 genes in the adenocarcinoma line Calu3. These results indicate that topoisomerase II alpha and ERBB2 may be closely linked on chromosome 17 and coamplified during adenocarcinoma progression. Since topoisomerase II is a target for several anticancer drugs, it will be of interest to study alterations to topoisomerase II genes during tumour development, as these may in part determine the response of the tumour to chemotherapy.
...
PMID:Amplification of the topoisomerase II alpha gene in a non-small cell lung cancer cell line and characterisation of polymorphisms at the human topoisomerase II alpha and beta loci in normal tissue. 137 18

The recent identification of the mouse White spotting and Steel loci as genes encoding the c-kit receptor and its ligand, respectively, has shed light on the importance of this ligand and receptor in embryogenesis, melanogenesis and hematopoiesis. In order to determine if the c-kit proto-oncogene is involved in human disease, we isolated seven overlapping lambda recombinants, using a fetal brain cDNA, and characterized the normal human gene (KIT). The longest mapped transcript is 5230 bp, is alternatively spliced and includes 21 exons that span more than 70 kb of DNA. From the exon-intron structure, we have localized an alternative splice site to the 3' end of exon 9. The overall c-kit gene structure closely resembles that found in the CSF-1R gene (c-fms). This similarity includes a large first intron, the same number of exons containing translated sequence and very similar exon-intron boundaries. Using pulsed-field gel electrophoresis, we have linked KIT to the platelet-derived growth factor receptor A gene, with both residing on a 700-kb BssHI fragment. These data will allow investigation into the control of KIT expression and the potential to identify mutations or altered expression of this gene in human disease.
...
PMID:Cloning and structural analysis of the human c-kit gene. 137 10

A characteristic balanced reciprocal chromosomal translocation [t(2;13)(q35;q14)] has been identified in more than 50% of alveolar rhabdomyosarcomas. As the first step in characterization of the genes involved in this translocation, we constructed somatic cell hybrids that retained either the derivative chromosome 2 or the derivative chromosome 13 without a normal chromosome 13 homologue. Ten linked DNA probes known to be located within bands 13q13-q14 were mapped relative to the breakpoint on chromosome 13, allowing localization of the breakpoint region between two loci separated by 5.5 cM. A long-range restriction map extending approximately 2,300 kb around these loci failed to provide evidence of rearrangement. Additionally, we confirmed that the FMS-like tyrosine kinase gene (FLT), previously localized to 13q12 by in situ hybridization, is located proximal to the breakpoint, and we demonstrated that FLT is not a target for disruption by this tumor-specific translocation.
...
PMID:Chromosomal sublocalization of the 2;13 translocation breakpoint in alveolar rhabdomyosarcoma. 138 66

The mutant human cell line 11.1 is unresponsive to interferon alpha. Here we describe the genetic complementation of this mutant and the identification and cloning of the wild-type gene that corrects the defect. Using transfection with genomic DNA in conjunction with a powerful back-selection, we isolated a cosmid that reverts the mutant phenotype of 11.1 cells. The cosmid encodes a single message whose level is greatly reduced in mutant cells. Complementary DNAs were cloned and found to be virtually identical to tyk2, a human mRNA encoding a non-receptor protein tyrosine kinase of previously unknown function. This finding shows that tyk2 links the interferon alpha/beta receptor to the cytoplasmic transcription factor that mediates activation of interferon-responsive genes.
...
PMID:A protein tyrosine kinase in the interferon alpha/beta signaling pathway. 138 89

We have compared spot-blot methodology with a recently developed rapid microtitre plate assay for the specific detection of HIV-1 PCR products. We have studied blood specimens isolated from HIV-1 infected individuals (48 asymptomatic and 56 symptomatic patients). Mononuclear cells were isolated, lysed and processed for PCR. Both PCR product detection methods were carried out in parallel on all amplified samples. HIV-1 sequences were detected by spot-blot or microtitre plate hybridization in samples taken from 42/48 asymptomatic and 53/56 symptomatic subjects. Concordant results between the two detection methods were observed for 90 samples, with 81 positive and nine negative assays. On repeat evaluation of the 14 discordant samples, nine showed concordant positive results, near the limit of detection of the assay. Serial dilutions of ACH-2 cells were amplified, and the PCR products were detected using the microtitre plate assay, yielding semi-quantitative results. The sensitivity of this simple, rapid assay compares with that of more laborious DNA detection systems. This may become a useful tool in HIV-1 research and in the clinical care of seropositive individuals.
...
PMID:Comparison of spot-blot and microtitre plate methods for the detection of HIV-1 PCR products. 140 33

Fibroblast growth factors (FGFs) and their receptors play an important role in cell growth, angiogenesis and embryonal development. Four distinct genes encoding fibroblast growth factor receptors (FGFRs) were identified: flg, encoding FGFR1, bek encoding FGFR2, and the genes for FGFR3 and FGFR4. Both FGFR2 and keratinocyte growth factor receptor (KGFR) are encoded by the same gene, bek. To study the regulation of expression of the FGF receptors we analysed the DNA sequence flanking the 5' region of the cDNA of murine FGFR2 to seek elements that control its transcription. A 5-kbp fragment containing the 5' end of the cDNA was isolated from mouse genomic library and used to map the promoter region. We found that the sequence encoding the 5' non-translated region of the FGFR2/KGFR cDNA contains an intron located 210 bp upstream from the translation start site. Using RNAase protection and primer extension, we identified the mRNA start 37 bp upstream from the beginning of the bek cDNA. The promoter activity was found to reside in a 1.3-kbp fragment upstream from the cDNA, and deletion mapping further localized the promoter to a 0.7-kbp fragment. The sequence of this region shows high G+C content (62%), which is particularly emphasized in the 200 bp upstream from the mRNA start (80% G+C). This region contains the CCGCCC, GGGCGG AND GGAGG motifs also found in promoters of other growth factor receptors. Neither TATA nor CAAT boxes were found near the RNA start site. The characterization of this promoter will allow studies of the regulation of expression of the FGFR2 during development and in pathophysiological states. The differences between the promoter sequence of the gene for FGFR2 (bek) and FGFR1 (flg) may explain their differential expression during development.
...
PMID:Promoter region of the murine fibroblast growth factor receptor 2 (bek/KGFR) gene. 140 37

We investigated the sequence requirements for ternary complex formation by the transcription factor SRF and its Ets domain accessory factors Elk-1 and SAP-1. Ternary complex formation is specified by an SRF consensus site CC(A/T)6GG and a neighbouring Ets motif (C/A)(C/A)GGA(A/T), which is contacted by Elk-1/SAP-1. Both the spacing of these sequences and their relative orientation can be substantially altered with little effect on the efficiency of ternary complex formation. Efficient ternary complex formation by Elk-1 is mediated by the B box, a conserved 21 amino acid region located 50 residues C-terminal to the Ets domain, which also acts to inhibit autonomous DNA binding. Binding studies with the isolated Ets domains indicate that ternary complex formation compensates for low affinity Ets domain-DNA interactions. Several naturally occurring SREs containing Ets motifs at different locations to that in the human c-fos SRE allow SAP-1 and Elk-1 recruitment in vitro. We discuss the mechanism of ternary complex formation.
...
PMID:Spatial flexibility in ternary complexes between SRF and its accessory proteins. 142 94

Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) play major roles in vertebrate embryogenesis, including control of skeletal muscle growth and differentiation. Understanding their roles requires delineating the specific FGF and FGFR isoforms involved. This study analyzes the FGFR transcripts found in a model mouse skeletal myoblast cell line (MM14) during growth and terminal differentiation. MM14 cells express transcripts for FGFR1 (flg) but not FGFR2 (bek). The predominate FGFR1 transcript contains three immunoglobulin (Ig)-like domains in the extracellular ligand binding region. Approximately one-fourth of the three Ig-like domain transcripts possess a 6-nt deletion between the first and second Ig-like domains which after translation would result in deletion of an Arg-Arg pair. Cloning of mouse genomic DNA surrounding the region of the FGFR1 6-nt deletion indicates that the deletion is derived by alternative splicing of FGFR1 transcripts. Transcripts containing two Ig-like domains account for less than 5% of total FGFR1 mRNA in MM14 cells. A survey of RNA from mouse tissues indicated that two Ig-like domain FGFR1 transcripts are rare in all tissues except in lung, in which the two Ig-like domain form accounts for roughly 70% of the lung FGFR1 mRNA. PCR RACE cloning studies disclosed 162 nt of additional FGFR1 5'-flanking RNA which was highly GC-rich. FGFR1 transcripts decline 8- to 10-fold during low serum, (-)FGF-mediated differentiation of MM14 cultures. The kinetics of the FGFR1 mRNA decline is similar to the previously described differentiation-dependent decrease in cell surface FGF receptors.
...
PMID:FGF-mediated aspects of skeletal muscle growth and differentiation are controlled by a high affinity receptor, FGFR1. 142 24

Chemoprevention trials in lung and upper aerodigestive tract (UADT) cancer are guided by the field cancerization hypothesis. Inhaled carcinogens place the entire epithelial lining at risk for the development of cancer. The hypothesis is supported by the occurrence of premalignant lesions, such as leukoplakia or squamous metaplasia, and multiple primary tumors within the field. The concept of carcinogenesis as a multistep process suggests the possibility of blocking or reversing the progression to invasive cancer with systemic treatment. A series of ongoing clinical trials will determine the efficacy of retinoid chemoprevention and will attempt to develop intermediate biomarkers. Biomarkers which reliably reflect progression towards cancer could be used to dramatically improve the efficiency of chemoprevention trials and also would aid in screening potential chemoprevention agents. Genomic biomarkers include non-specific estimates of ongoing DNA injury, such as micronuclei, as well as development of aneuploidy and alterations in oncogenes. A class of biomarkers of increasing importance assess proliferation and growth regulation, and include proliferating cell nuclear antigen (PCNA), TGF-beta, EGFR and retinoid receptors. Other markers, such as the blood group antigens, reflect differentiation and may be associated with the development of premalignant lesions. Preliminary data from several of these markers has suggested an association with carcinogenic exposures and premalignant lesions, but none of these markers either alone or in panels have yet been validated as a reliable surrogate for the development of invasive cancer.
...
PMID:Intermediate biomarkers in upper aerodigestive tract and lung chemoprevention trials. 146 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---