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:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously established transplantable rat thyroid carcinoma cell lines in vivo from primary thyroid tumors induced by N-bis-(2-hydroxypropyl)nitrosamine (DHPN). In the present study, an insulin-like growth factor I (IGF-I)-responsive cell line (TRTC-G1-C-A4) in culture was derived from one (well differentiated papillary type) of these carcinoma cell lines G1. TRTC-G1-C-A4 cells were found to exhibit specific saturable binding of IGF-I with a Kd of 1.16 nM at approximately 43.6 fmol/10(5) cells. Inclusion of IGF-I (10 and 50 ng/ml) in the culture medium resulted in a significant increase of [3H]thymidine incorporation and marked cell proliferation. IGF-II (10 ng/ml) and insulin (1 microgram) produced no such effects. The molecular weight of IGF-I receptors on the cell membrane was determined by Western blotting analysis, a single band of binding proteins with a molecular weight of 125 kDa being evident under non-reducing conditions. Reverse transcriptase polymerase chain reaction (RT-PCR) showed that the TRTC-G1-C-A4 cells contained IGF-I receptor mRNA with a sequence corresponding to that determined from rat uterus. These results demonstrate that the IGF-I receptor can be expressed in a thyroid carcinoma with an important contribution to cell growth.
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PMID:Establishment of a rat thyroid carcinoma cell line in vitro demonstrating high DNA synthesis in response to insulin-like growth factor I. 862 Apr 77

A macromolecular fraction was isolated from ovine bone marrow and designated the active fraction (AF). Two distinct enzymatic activities were detected in the AF: (1) a RNA-dependent RNA polymerase, and (2) a reverse transcriptase. RNA polymerase uses an endogenous RNA molecule of the AF as the template while the product of this RNA polymerase reaction forms the template for the reverse transcriptase. Synthetic reactions are initiated exclusively upon the exposure of the in vitro system to one of the external proteins, selected at random, ovalbumin or insulin. Ovalbumin specific (OS) and insulin specific (IS) AF fractions were prepared. OS-AF binds 14C-ovalbumin and the IS-AF binds 14C-insulin, but not vice versa. Reverse transcription activity of OS-AF is stimulated only upon its exposure to ovalbumin and not to insulin while the reverse is true for the activity associated with IS-AF. Indirect evidence indicates that the enzymes which synthesize nucleic acids are closely associated with the antigen receptor on the B-lymphocyte plasma membrane, the mlgM, and that the antigen binding to its receptor helps in the activation of these enzymes.
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PMID:Reverse transcription in a macromolecular complex of ovine bone marrow: possible involvement in the antigen receptor mediated signal transduction process. 868 97

The effects of retinoic acids (RAs) on development of seminal vesicles (SVs) of neonatal mice were investigated in vitro. SVs from 0-day-old male mice were cultured for 2-6 days in serum-free, chemically defined medium containing transferrin and BSA supplemented with 5alpha-dihydrotestosterone (DHT; 10(-8) M) and insulin (10 microg/ml), alone and in combination. Before culture, SVs from 0-day-old mice consisted of an unbranched epithelium surrounded by mesenchyme. SVs cultured in medium with DHT plus insulin or DHT alone formed numerous epithelial branches after day 2 of culture, whereas epithelial branching did not occur in SVs cultured with insulin alone. All-trans-RA or 13-cis-RA (10(-9)-10(-6) M) added to medium containing DHT plus insulin or DHT alone inhibited epithelial branching in a dose-dependent manner. This inhibitory effect was reversible after removal of the retinoids from the medium on day 4 of culture. These RAs also decreased [3H]thymidine labeling indexes of both epithelium and mesenchyme of SVs cultured in medium with DHT plus insulin or DHT alone and inhibited the increase in their protein contents. 9-Cis-RA was less inhibitory than all-trans-RA or 13-cis-RA on epithelial branching, [3H]thymidine labeling indexes of epithelium and mesenchyme, and protein content of SVs cultured in medium with DHT and insulin. In the absence of DHT (insulin alone), all-trans-RA did not affect either the [3H]thymidine labeling indexes of epithelium and mesenchyme or the protein content of cultured SVs. Reverse transcriptase-PCR demonstrated strong expression of transcripts for mouse RA receptors (RARalpha, RARgamma, and RXRalpha), with lower levels of expression of RARbeta, RXRbeta, and RXRgamma in neonatal SVs. The present results indicate that RAs reversibly inhibit androgen-dependent development of neonatal mouse SVs, most likely through RARs.
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PMID:Inhibitory effects of retinoic acids on androgen-dependent development of neonatal mouse seminal vesicles in vitro. 877 Sep 10

1. There are two functionally different isoforms of the insulin receptor in humans and rats. We hypothesized that a change in their relative proportion could be of relevance to insulin resistance in hypertension. 2. A reverse-transcriptase polymerase chain reaction technique was established for the detection of mRNA for the exon 11+ and exon 11- isoforms and the proportion of each was determined in 3, 6, 9 and 12 week old spontaneously hypertensive rats and Wistar-Kyoto rats, as well as adrenocorticotrophin (ACTH)-induced hypertensive rats and controls. 3. The proportion of the exon 11+ form (approximately 95%) and exon 11- form (approximately 5%) was similar in the liver of all rats studied. 4. We conclude that there is no change in insulin receptor isoform expression in the liver in the models of hypertension studied.
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PMID:No difference in the proportion of insulin receptor exon 11 +/- isoform mRNA in the liver of rats after development of hypertension. 880 May 98

Cholecystokinin (CCK) has been suggested to modulate insulin output. We have shown that Otsuka Long-Evans Tokushima Fatty (OLETF) rats show little or no expression of the CCK-A receptor gene in the pancreas. We examined whether the CCK-A and CCK-B receptor genes are expressed in the islets and the role of CCK-A receptor in insulin secretion. Gene expressions of CCK receptors were determined by the reverse-transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization and Northern transfer analysis using LETO rats as controls. Pancreatic endocrine function was examined in perfusion (exogenous CCK stimulation) and meal ingestion (endogenous CCK stimulation) studies. CCK-A receptor mRNA was detected in the islets of LETO rats but not OLETF rats. Expression of the CCK-B receptor gene was detected in both strains by RT-PCR. Insulin secretion was impaired in OLETF rats, but the insulin contents of OLETF and LETO rats were not different. No abnormalities were detected histologically in either strain. These results suggest that the occurrence of pancreatic endocrine dysfunction in OLETF rats may be due to a defect in expression of the CCK-A receptor gene, not to insulin deficiency.
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PMID:Pancreatic endocrine dysfunction in rats not expressing the cholecystokinin-A receptor. 883 Mar 28

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel neuropeptide that produces its biological effects by interacting with G protein-coupled receptors. Molecular cloning of the PACAP receptor revealed the existence of five splice variant receptor forms differing in the third intracellular loop region, with four variants activating both adenylyl cyclase and phosphoinositide phospholipase C and one variant activating only adenylyl cyclase (Spengler, D., Waeber, C., Pantaloni, C., Holsboer, F., Bockaert, J., Seeburg, P. H., and Journot, L. (1993) Nature 365, 170-175). Here, we report cloning of a novel PACAP receptor variant, designated PACAPR TM4 (transmembrane domain IV), that differs from the previously cloned short form of the PACAP receptor (PACAPR) primarily by discrete sequences located in transmembrane domains II and IV. Reverse transcriptase-polymerase chain reaction and primer extension analyses demonstrated tissue-specific differential expression of mRNAs encoding PACAPR TM4 and splice variant forms of the PACAP receptor. PACAPR TM4 and PACAPR possess identical intracellular domains, implicated as primary determinants of G protein recognition by rhodopsin-like receptors. However, unlike the PACAPR, PACAPR TM4 does not activate either adenylyl cyclase or phosphoinositide phospholipase C in response to PACAP in either transient or stable expression systems. However, PACAP stimulates increases in [Ca2+]i in cells expressing PACAPR TM4 by activating L-type Ca2+ channels, a response not elicited by stimulation with vasoactive intestinal polypeptide. The signaling phenotype of PACAPR TM4 is characteristic of the PACAP receptor involved in regulation of insulin secretion from pancreatic beta islets, a tissue expressing transcripts for PACAPR TM4 but not for PACAPR or its longer splice variant forms. These findings are consistent with a role of PACAPR TM4 in the physiological control of insulin release by PACAP in beta-islet cells. The finding that PACAPR TM4 has a unique signaling phenotype, although it possesses intracellular domains identical to those of the PACAPR, suggests that receptor-G protein recognition by rhodopsin-like receptors can be determined by sequences other than those located in intracellular receptor domains.
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PMID:Molecular cloning of a novel variant of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor that stimulates calcium influx by activation of L-type calcium channels. 894 80

Chinese hamster ovary cells (CHO cells) do not exhibit any Ca2+/calmodulin-stimulated cAMP phosphodiesterase (PDE1) activity. Challenge of CHO cells with agonists for endogenous P2-purinoceptors, lysophosphatidic acid receptors and thrombin receptors caused a similar rapid transient induction of PDE1 activity in each instance. This was also evident on noradrenaline challenge of a cloned CHO cell line transfected so as to overexpress alpha 1B-adrenoceptors. This novel PDE1 activity appeared within about 15 min of exposure to ligands, rose to a maximum value within 30 min to 1 h and then rapidly decreased. In each case, the expression of novel PDE1 activity was blocked by the transcriptional inhibitor actinomycin D. Challenge with insulin of either native CHO cells or a CHO cell line transfected so as to overexpress the human insulin receptor failed to induce PDE1 activity. Reverse transcriptase-PCR analyses, using degenerate primers able to detect the PDE1C isoform, did not amplify any fragment from RNA preparations of CHO cells expressing PDE1 activity, although they did so from the human thyroid carcinoma FTC133 cell line. Reverse transcriptase-PCR analyses, using degenerate primers able to detect the PDE1A and PDE1B isoforms, successfully amplified a fragment of the predicted size from RNA preparations of both CHO cells expressing PDE1 activity and human Jurkat T-cells. Sequencing of the PCR products, generated using the PDE1A/B primers, yielded a novel sequence which, by analogy with sequences reported for bovine and murine PDE1B forms, suggests that the PDE1 species induced in CHO cells through protein kinase C activation and that expressed in Jurkat T-cells are PDE1B forms.
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PMID:Receptor-mediated stimulation of lipid signalling pathways in CHO cells elicits the rapid transient induction of the PDE1B isoform of Ca2+/calmodulin-stimulated cAMP phosphodiesterase. 900 15

cDNA clones encoding human (h) Grb7 and a previously unknown protein with high homology to hGrb-IR and mGrb10 (where m indicates mouse) were found by screening expressed sequence tag data bases. hGrb7 mRNA expression is greatest in pancreas and restricted to a few other tissues. The second protein termed hGrb-IRbeta/Grb10 contains an intact PH domain and lacks the 80-residue mGrb10 insertion. Expression is greatest in pancreas and muscle but occurs in nearly all tissues. hGrb-IRbeta/Grb10 and hGrb-IR likely arise as alternative mRNA splicing products of a common gene. Reverse transcriptase-coupled polymerase chain reaction shows both mRNAs in muscle. In cells, Grb-IRbeta/Grb10 protein translocates from cytosol to membrane upon insulin stimulation, most likely due to direct interactions with the insulin receptor. These interactions are mediated by the SH2 domain and additional regions of the protein. Studies with mutated receptors and synthetic phosphopeptides show that the hGrb-IRbeta/Grb10 SH2 domain binds at least two sites in the insulin receptor: the kinase activation loop > the juxtamembrane site. hGrb-IRbeta/Grb10 also binds a 135-kDa phosphoprotein in unstimulated 3T3-L1 adipocytes; binding is reduced upon insulin stimulation. In addition, the c-Abl SH3 domain binds Grb-IR/Grb10, whereas Fyn, phosphatidylinositol 3-kinase p85, and Grb2 SH3 domains do not. The site of c-Abl SH3 domain interaction is highly conserved within the Grb-IR/Grb10/Grb7/Grb14 family. hGrb-IRbeta/Grb10 also binds platelet-derived growth factor and epidermal growth factor receptors, suggesting a broader role in the signaling pathways of numerous receptors. We conclude that hGrb-IRbeta/Grb10 is a widely expressed, PH and SH2 domain-containing, SH3 domain-binding protein that functions downstream from activated insulin and growth factor receptors.
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PMID:Human GRB-IRbeta/GRB10. Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains. 900 1

Insulin-response glucose transporter GLUT4 is a member of the glucose transporter family (GLUT) and is present exclusively in muscle and adipose tissue. It is a target of insulin action in humans and rodents. To clarify the molecular structure of bovine GLUT4, its GLUT4 cDNA was cloned by the RT-PCR method. Several cDNA clones corresponding to the different regions of GLUT4 were obtained by amplifying reverse-transcriptase products of RNA extracted from Holstein cattle skeletal muscle. Nucleotide sequence analysis of the cDNA clones revealed that bovine GLUT4 cDNA was composed of 2,656 base pairs with a coding region for a 509 amino acid protein. The deduced amino acid sequence was 64% and 92% identical with bovine GLUT1 (GLUT ubiquitously expressed in all tissues) and rat GLUT4, respectively. Although the amino acid sequence of the GLUT4 COOH-terminal region is highly conserved among the species so far reported, one amino acid (Asp) of the region was replaced by His in bovine GLUT4. The tissue distribution of GLUT4 was also examined by Northern blot analysis using a probe prepared from the bovine cDNA. GLUT4 mRNA was detected in skeletal muscle, heart, and adipose tissue, but not in liver, kidney, lung, brain, or spleen. Such a distribution is essentially the same as in humans and rodents, suggesting that GLUT4 is an insulin-responsive glucose transporter in cattle.
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PMID:Molecular cloning and mRNA expression of the bovine insulin-responsive glucose transporter (GLUT4). 902 64

The principal goal of the present study was to test the hypothesis that cytokines modulate glucose transport in skeletal muscle by increasing nitric oxide production. Cultured L6 skeletal muscle cells were incubated in the presence of tumour necrosis factor-alpha, interferon-gamma or lipopolysaccharide (LPS) alone or in combination for 24 h. Neither cytokines nor LPS alone induced NO production, as measured by nitrite concentrations in the medium. However, when used in combination, the two cytokines significantly stimulated NO production, and this effect was synergistically enhanced by the presence of LPS. Reverse transcriptase-PCR (RT-PCR) analysis revealed that NO release was associated with the induction of inducible (macrophage-type) NO synthase (iNOS). The increase in iNOS expression was confirmed at the protein level by Western-blot analysis and NADPH/diaphorase histochemical staining. Cytokines and LPS markedly increased basal glucose transport in L6 myocytes. Insulin also stimulated basal glucose transport, but significantly less in cells chronically exposed to cytokines/LPS. The sensitivity of L6 muscle cells to insulin-stimulated glucose transport was also significantly decreased by cytokines/LPS treatment. The NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME) inhibited nitrite production in cytokine/LPS-treated cells, and this prevented the increase in basal glucose transport and restored muscle cell responsiveness to insulin. Cytokines/LPS exposure significantly increased GLUT1 transporter protein levels but decreased GLUT4 expression in L6 cells. l-NAME treatment prevented the increase in GLUT1 protein content but failed to restore GLUT4 transporter levels. These results demonstrate that cytokines and LPS affect glucose transport and insulin action by inducing iNOS expression and NO production in skeletal muscle cells. The data further indicate that cytokines and LPS increase the expression of the GLUT1 transporter protein by an NO-dependent mechanism.
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PMID:Cytokines modulate glucose transport in skeletal muscle by inducing the expression of inducible nitric oxide synthase. 923 Jan 32


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