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)

Heparan sulfate proteoglycans are thought to be obligatory for receptor binding and subsequent mitogenic activity of basic fibroblast growth factor (FGF-2). In a previous study (Nurcombe V., Ford, M. D., Wildschut, J., Bartlett, P. F. (1993) Science 260, 103-106) we have shown that primary cultures of mouse neuroepithelial cells and a cell line derived from then, 2.3D, secrete a heparan sulfate proteoglycan with a high affinity for FGF-2. In this study, a combination of affinity chromatography and gel chromatography was used to further isolate heparan sulfate side chains with high affinity for FGF-2. These active chains had an average molecular weight of 18,000-20,000. In order to determine whether heparan sulfate chains with specificity for FGF-2 also displayed selectivity for the different FGF receptors, peptides designed to the heparin-binding region of the receptors were used in competitive inhibition studies. The structure of the predicted heparin-binding domain of the FGF receptor 1 was modeled on the basis of its presumed secondary and tertiary structure homology with immunoglobulin loops. These results suggested that many of the basic residues within the second immunoglobulin loop of the FGF receptor 1 form a basic domain in the molecule and therefore form part of a heparin-binding site. Peptides homologous to this region of FGF receptor 1 were shown to inhibit mitogenesis in 2.3D cells, while those to FGF receptor types 2, 3, and 4 did not. A reverse transcriptase-polymerase chain reaction assay designed to detect expression of the four FGF receptors types demonstrated that FGF receptors 1 and 3 were present on the 2.3D cell line but that receptors 2 and 4 were not. These findings indicate that unique heparan sulfate domains interact with specific cell-surface receptors to direct cellular responses.
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PMID:Heparan sulfates mediate the binding of basic fibroblast growth factor to a specific receptor on neural precursor cells. 755 20

Keratinocyte growth factor (KGF) is synthesized and secreted exclusively by mesenchymal cells, and acts through its receptor (KGFR) to stimulate epithelial proliferation. In vivo, KGF and KGFR comprise a mesenchymal-epithelial cell paracrine system that can mediate epithelial cell mitosis. In preliminary work, we noted that KGF was expressed in the rhesus monkey placenta, and we now report on the expression of placental KGF and KGFR mRNAs during the course of gestation in this species. In-situ hybridization revealed that during early gestation, KGF mRNA was strongly expressed in placental mesenchymal cells. These cells, which were also immunoreactive for vimentin, were mainly located on the periphery of the mesenchymal cores of both anchoring and floating villi. KGFR mRNA was expressed in the adjacent trophoblastic epithelium, which was immunoreactive for cytokeratin. In-situ hybridization revealed that KGF mRNA expression was very high in the youngest placentae (34-days gestation) and decreased gradually to minimal levels by late gestation (157 days). Northern blot analysis indicated also that the KGF MRNA signal was strongest in early gestation samples and weakest by late gestation. Analysis for KGFR mRNA by a reverse transcriptase-polymerase chain reaction technique showed that KGFR mRNA expression could be detected at all stages. However, in-situ hybridization indicated that KGFR mRNA expression was highest in early gestation placentae and least in the oldest placentae. Autoradiographs of frozen sections of placenta that had been incubated with [125I]KGF to detect receptor binding showed that grain density over the trophoblast was highest in the youngest and least in the oldest placentae. PCNA and Ki-67 expression followed this same temporal trend. We conclude that the KGF/KGFR system may be important in proliferation of the placental trophoblast during early- to mid-pregnancy in rhesus monkeys.
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PMID:Keratinocyte growth factor and its receptor in the rhesus macaque placenta during the course of gestation. 873 Aug 82

Previous studies have indicated that growth factors such as epidermal growth factor, transforming growth factor alpha, and fibroblast growth factor 1 (FGF-1) have important regulatory functions in murine urothelial wound healing and tumorigenesis. Immunocytochemical analyses suggest that these factors are also involved in human urothelium. Yet, little is known about the functional effects of these growth factors on human urothelial cells. We established organoid-like primary cultures of normal human urothelium on porous membranes. Direct functional effects of growth factors were examined on confluent cultures reflecting intact urothelium. Immunocytochemistry was performed with a panel of specific antibodies against growth factors and their receptors on both cultures and the corresponding tissue sections. Lacking the appropriate antibodies, we performed reverse transcriptase PCR to detect FGF receptor mRNA in cultures and dissected tissue. The proliferation was stimulated by transforming growth factor alpha, FGF-1, and weakly by FGF-7, but not by FGF-2. TGF beta 1 inhibited proliferation. In contrast to mouse urothelium, none of the growth factors showed an effect on differentiation. The functional data correlate with the urothelial expression of epidermal growth factor receptors, TGF beta receptor types I and II, the (low) protein expression of FGF receptor 1, and the presence of FGF-7 receptor (FGF receptor 2 (IIIb)) mRNA. The organotypic nature of the cultures permits the study of growth factor interactions between urothelial cells. The data indicate that FGF-1, transforming growth factor alpha, and TGF beta 1 contribute differently to the maintenance of human urothelium.
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PMID:Functions of fibroblast and transforming growth factors in primary organoid-like cultures of normal human urothelium. 876 15

Sensory epithelia from normal rat utricles and those cultured with and without neomycin treatment were assayed for the presence of growth factor receptor mRNAs by RT-PCR (reverse transcriptase-polymerase chain reaction). Both undamaged and damaged utricles showed mRNA for Insulin receptor, IGF-I receptor, FGF receptor 1, EGF receptor, and PDGF alpha receptor. Neomycin-damaged sensory epithelia showed less PDGF alpha receptor mRNA than undamaged epithelia, suggesting that this message by expressed at higher copy levels in hair cells than in supporting cells. Consistent with that hypothesis, immunohistochemistry revealed much stronger PDGF alpha receptor staining in the hair cells than in the supporting cells. Preliminary evidence suggests that IGF-I receptor message also may be lowered in neomycin-damaged epithelia.
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PMID:An RT-PCR analysis of mRNA for growth factor receptors in damaged and control sensory epithelia of rat utricles. 878 7

The expression of mRNA encoding alternative forms of fibroblast growth factor receptor 2 (FGFR2) differing in the carboxy terminal half of their third immunoglobulin-like domain, was investigated in 77 human breast cancer tissues, 12 non-malignant breast biopsies and 29 cell lines, using a reverse transcriptase (RT) polymerase chain reaction (PCR) method. RNA from the two tissue groups yielded PCR product corresponding to both the BEK and the K-SAM form; amounts normalised to glyceraldehyde phosphate dehydrogenase product were similar in both groups. The level of either variant or of the total FGFR2 product was essentially unrelated to prognosis or clinical status except that patients with advanced clinical T staging had a higher proportion of BEK to K-SAM (P = 0.01). RNA from 1/2 normal breast derived and 8/10 breast cancer cell lines expressed exclusively or predominantly the K-SAM form; 2/10 had significant amounts of both BEK and K-SAM mRNA. Of 12 other epithelial lines, seven expressed mainly K-SAM mRNA, four expressed BEK and one was negative. Of five non-epithelial lines, one was negative, two expressed only BEK mRNA and two had significant amounts of both variants. We conclude that tissue levels of FGFR2 mRNA are unaltered in breast cancer extracts and that the splicing mechanism for this exon selection appears not to be significantly disrupted.
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PMID:Expression of FGFR2 BEK and K-SAM mRNA variants in normal and malignant human breast. 881 1

The level of expression of keratinocyte growth factor (KGF) mRNA has been measured in human breast cell lines, purified populations of epithelial cells, myoepithelial cells and fibroblasts from reduction mammoplasty tissue and a panel of 42 breast cancers and 30 non-malignant human breast tissues using a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) procedure. We found similar levels of KGF mRNA in malignant and non-malignant breast tissues. The study of the amount of KGF mRNA in breast cell lines and purified populations of cells revealed that fibroblasts are the predominant source of KGF with malignant and non-malignant epithelial cells containing very low levels of KGF mRNA. We have examined the distribution of fibroblast growth factor receptor (FGFR)-2-IIIb, which is a high-affinity receptor for KGF and find that it is present on malignant and non-malignant epithelial cells. The level of FGFR-2-IIIb present on breast cancer cell lines was sufficient for KGF stimulation of breast cancer cell proliferation. Other members of the fibroblast growth factor family have been either not expressed in the human breast (FGF3, FGF4) or have been found at much reduced levels in breast cancer (FGF1, FGF2) and this is the first member of the family to potentially influence the progression of breast cancer through stimulation of cell division.
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PMID:Expression of keratinocyte growth factor and its receptor in human breast cancer. 918 70

Basic fibroblast growth factor (bFGF) and its specific receptors have diverse roles on a variety of cell types, such as the induction of vascular smooth-muscle cell proliferation which contributes to restenosis after coronary balloon angioplasty. bFGF is also known to interact with heparan sulphate proteoglycans present on the cell surface or in the extracellular matrix. In this study, the binding of 125I-bFGF to human aortic smooth-muscle cells was investigated. 125I-bFGF binding to these cells was reversible and saturable. Scatchard analysis revealed the presence of two distinct binding sites: a high-affinity receptor (Kd=38+/-7 pM; 1480+/-220 sites/cell) and a low-affinity non-saturable binding site (Kd=8. 0+/-2.0 nM). Pretreatment of the cells with heparinase resulted in a large reduction of 125I-bFGF binding to its low-affinity receptors, suggesting that they are heparin-like molecules. The specificity of the low- and high-affinity binding sites for bFGF was determined with acidic FGF, platelet-derived growth factor-BB and epidermal growth factor, which did not compete for 125I-bFGF binding. Expression of FGF receptor isoforms analysed by reverse transcriptase-PCR revealed the presence of only the type-1 receptor. Binding to low-affinity binding sites was antagonized by heparin, suramin, protamine sulphate and platelet factor 4. Unexpectedly, these molecules also reduced the binding of 125I-bFGF to its high-affinity sites. Consistent with these results, heparin, suramin, protamine sulphate and platelet factor 4 inhibited bFGF-induced proliferation of human aortic smooth-muscle cells. Heparin abrogated bFGF-induced release of tissue-type plasminogen activator by these cells. These observations suggest that the interaction of bFGF with human aortic smooth-muscle cells is different from that described for other cells such as endothelial cells, in which heparin acts as a potentiating factor of the mitogenic activity of bFGF.
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PMID:Heparin inhibits the binding of basic fibroblast growth factor to cultured human aortic smooth-muscle cells. 930 14

Satellite cells isolated from fast tibialis anterior (TA) and slow soleus (SOL) rat muscles were cultivated on matrigel, and treated with acidic fibroblast growth factor (aFGF). The following observations were made: 1) aFGF-treated cultures exhibited enhanced proliferation as mirrored by a twofold increase in DNA content. 2) Compared to the untreated cultures, myotubes in the aFGF cultures were larger; 3) Using reverse transcriptase polymerase chain reaction (RT-PCR) and northern blot analyses, we observed enhanced expression of all adult myosin heavy chain (MHC) isoforms, as well as of myogenin. These findings indicate that, under the culture conditions used, aFGF has a stimulatory effect on proliferation but also on maturation and differentiation of satellite cells. Furthermore, transcript levels of FGF receptor 1 (FGFR1) and 4 (FGFR4) isoforms, as well as of aFGF and bFGF were assessed by RT-PCR. aFGF-treated myotubes displayed increased expression of aFGF and bFGF, suggesting a paracrine effect of exogenous aFGF. In this regard, SOL-derived cultures responded more strongly than TA-derived cultures. The effects of aFGF treatment on the two receptors consisted of a decrease in FGFR1 and an increase in FGFR4 mRNA levels in 5-day-old cultures. In 8-day-old TA cultures, effects of FGF were similar to those in 5-day-old cultures. 8-day FGF-treated SOL cultures treated with FGF for 8 days exhibited higher FGFR1 and FGFR4 mRNA levels than the respective untreated cultures. Compared to 5 day-treated cultures, FGFR1 increased and FGFR4 decreased. This led to a shift in the ratio of FGFR1 to FGFR4 in the FGF-treated cultures which may explain the ability of satellite cells to differentiate under the influence of aFGF.
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PMID:Evidence that acidic fibroblast growth factor promotes maturation of rat satellite-cell-derived myotubes in vitro. 1063 13

Fibroblast growth factors (FGFs) are a family of heparin binding proteins involved in many biological processes. These growth factors act through tyrosine kinase receptors (FGFRs); we have previously used immunohistochemistry to study FGFRs-1-4 in foetal, immature and adult rat testes, and found a discrete cell- and stage-specific localisation. Alternative mRNA splicing of FGFRs-1-3 leads to functional variants (IIIb and IIIc) with distinct ligand binding affinities, therefore we have identified the specific expression of functional FGFR variants and the expression and localisation of FGF ligands in testes from foetal, immature and adult rats. Using reverse transcriptase-polymerase chain reaction (RT-PCR), we found that mRNAs for FGFR-1 IIIb and IIIc, FGFR-2 IIIc, FGFR-3 IIIc and FGFR-4 were expressed in foetal, immature and adult testes. Ligands FGFs-1-5, and -8, which can signal through these receptors, were also expressed in testes at each age. Localisation of the ligands FGFs-1, -3 and -4 to rat testes by immunohistochemistry showed a discrete cell- and stage-specific localisation that altered during testis development. This study has shown that the ligands FGFs-1, -3 and -4 are expressed in the testis and have the capacity to signal through appropriate receptors that are also co-localised or expressed in adjacent cell types in the testis. Collectively, the expression profiles of the seven FGFR variants and FGFs-1-5 and -8 suggest a functional importance in testicular development and spermatogenesis. It is concluded that, future studies on the role of other FGF ligands, in particular FGFs-1-4, are warranted.
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PMID:Discrete cell- and stage-specific localisation of fibroblast growth factors and receptor expression during testis development. 1065 50

In this study the mRNAs encoding epidermal growth factor receptor (EGFR), basic fibroblast growth factor receptor (FGFR-2) and insulin-like growth factor receptor (IGFR-1) genes of the human normal lenses at ages varying from 0.5 to 72 years, were identified by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Regulation of EGFR gene expression in the lens did not change with aging, and of FGFR-2 and IGFR-1 genes also remained unaltered up to age 53 years. However, expressions of FGFR-2 and IGFR-1 genes were decreased at ages above 60 years. EGFR, FGFR-2 and IGFR-1 proteins were detected by immunoblot analysis in the epithelial cell membranes of lens at age varying from 40 to 72 years. There was no detectable amount of EGFR protein in fiber cell membranes of the lens, and the levels of FGFR-2 and IGFR-1 proteins were much lower than those in the epithelial cell membranes. The low levels of these receptor proteins in the fiber cell membranes of lens, suggest their possible role in keeping the differentiated function of these unique transparent cells. The findings of the increased protein levels with age of EGFR with the appearance of some degradation products at age 48 years and higher, and the increased FGFR-2 protein at age 60 years and higher in the epithelial cell membranes of lens, were of interest. It appears that this could be a compensatory protective response of the lens to aging process for lifelong continuation of normal growth by proliferation and differentiation of its epithelial cells into new fiber cells in the germinative zone at the equatorial region. Thus, these results could provide a basis for further studies on growth factor receptor gene and protein regulations in the mechanism of lens aging and progression of age-related human cataract.
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PMID:Growth factor receptor gene and protein expressions in the human lens. 1071 39


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