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)

The biological activity of insulin-like growth factor-I (IGF-I) is mediated by a transmembrane glycoprotein (type-1 IGF receptor or IGF-I receptor) that shows considerable sequence homology with the insulin receptor. In order to detect the expression of this gene in chicken liver tissue, a plasmid was constructed containing a fragment of chicken IGF-I receptor cDNA. The cDNA fragment corresponded to nucleotides 326-599 of the human IGF-I receptor cDNA and showed 86.1 and 69.3% homology at the nucleotide level and 96.7 and 80.2% homology at the amino acid level with the human IGF-I receptor and insulin receptor respectively. The construct was used to generate an antisense RNA probe for the detection of IGF-I receptor mRNA transcripts in 1- and 4-week-old chick liver tissue. IGF-I receptor gene expression was initially detected by the reverse transcriptase polymerase chain reaction using synthetic chicken IGF-I receptor oligonucleotides. Amplified fragments of the correct size were detected in both RNA samples. Northern blots were also used to detect IGF-I receptor mRNA transcripts in the liver RNA samples. The results indicated that the amount of receptor mRNA decreased significantly between 1 and 4 weeks after hatch. In contrast, chicken beta-actin gene expression remained constant over this period. A major IGF-I receptor RNA transcript (11 kb) was observed in blots from 1-week-old livers, less abundant transcripts were also observed ranging in size from 8 to 9 kb.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The expression of a putative insulin-like growth factor-I receptor gene in the liver of the developing chick. 132 34

The insulin receptor possesses tyrosine kinase activity which is thought to mediate the biological effects of insulin upon target cells. pp120 is a liver-specific glycoprotein of apparent molecular size of 120 kDa that is phosphorylated on tyrosine residues by the receptors for insulin, insulin-like growth factor-I, and epidermal growth factor. Previously, we demonstrated that pp120 is identical to a liver-specific ecto-ATPase. In the present study, we have cloned the rat gene encoding pp120/ecto-ATPase. The gene is contained within approximately 15 kilobases of genomic DNA, and consists of nine exons interrupted by eight introns. Using the reverse transcriptase/polymerase chain reaction, we isolated cDNA clones complementary to rat liver mRNA encoding pp120/ecto-ATPase. Sequence analysis indicated the presence of two populations of cDNA's that differ by the presence or absence of a 53-base pair (bp) fragment encoding the juxta-membrane region of the cytoplasmic domain. By cloning the corresponding region of the ecto-ATPase gene, we demonstrated that the 53-bp represents exon 7 of the gene. This 53-bp exon undergoes alternative splicing, thereby giving rise to two mRNA variants. Deletion of this 53-bp cassette exon introduces a frameshift, and results in a premature chain termination codon that truncates the cytoplasmic domain. The truncated cytoplasmic domain contains 10 rather than 71 amino acid residues. Because the short isoform of ecto-ATPase lacks the putative sites for tyrosine- and serine-specific phosphorylation, this alternative splicing may have a major effect upon the physiological function of the enzyme.
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PMID:pp120/ecto-ATPase, an endogenous substrate of the insulin receptor tyrosine kinase, is expressed as two variably spliced isoforms. 838 Apr 6

The expression of insulin receptor mRNA was examined in rat pancreatic islet cells by single-cell reverse transcriptase (RT)-polymerase chain reaction (PCR). Single cells from disaggregated islets were individually isolated in a microcapillary pipet, and the beta-cells were identified by amplification of the mRNA for insulin. We found that in single beta-cells, the mRNA for the insulin receptor was also expressed. The fraction of single islet cells expressing both insulin receptor and insulin mRNAs corresponds closely to the fraction of beta-cells in the disaggregated islet cell preparation. These results indicate that normal beta-cells have the potential to express authentic insulin receptors. Immunohistochemical analysis was insufficiently sensitive for assaying insulin receptor protein; however, insulin receptor substrate 1 (IRS-1) was readily immunolocalized in islet beta-cells. Since IRS-1 links several cell surface receptors, including those for insulin and IGF-I, to distal signal transduction pathways, our observations indicate that hormonal regulation of islet beta-cells potentially involves the same signal transduction pathway that mediates insulin and growth factor signaling in peripheral insulin target tissue cell types.
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PMID:Expression of insulin receptor mRNA and insulin receptor substrate 1 in pancreatic islet beta-cells. 863 42

Alternative splicing of the 36-base pair exon 11 of the human insulin receptor gene results in the synthesis of two insulin receptor isoforms with distinct functional characteristics (the isoform containing exon 11 has lower insulin binding affinity and lower internalization rate). Altered expression of these insulin receptor isoforms has been previously demonstrated in skeletal muscle of patients with non-insulin-dependent diabetes mellitus (NIDDM). However, this observation was not confirmed by other studies and is still a matter of controversy; furthermore, it is not known whether it represents a primary event or is secondary to hyperinsulinaemia and insulin resistance. In order to address this issue in patients with pure non-genetically determined hyperinsulinaemia, we examined the alternative splicing of insulin receptor mRNAs in skeletal muscle of eight patients with surgically confirmed insulinoma and insulin resistance and in eight healthy subjects, using the reverse transcriptase-polymerase chain reaction technique. The insulinoma patients displayed a significant increase in the expression of the insulin receptor isoform containing exon 11 (75.7 +/- 2.3%) when compared with normal subjects (57.9 +/- 1.5%); furthermore, this increase was positively correlated with plasma insulin concentration and negatively correlated with in vivo insulin sensitivity (glucose clamp). In conclusion, the increased expression of the insulin receptor isoform with lower insulin binding affinity in patients with primary non-genetically determined hyperinsulinaemia supports a role for insulin in the regulation of alternative splicing of insulin receptor pre-mRNA and suggests that in NIDDM an altered receptor isoform distribution might be secondary to the ambient hyperinsulinaemia rather than representing a primary defect.
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PMID:Chronic primary hyperinsulinaemia is associated with altered insulin receptor mRNA splicing in muscle of patients with insulinoma. 863 75

Messenger RNAs (mRNA) of several growth factor receptors and relate genes were examined with reverse transcriptase polymerase chain reaction (RT-PCR) in normal and noise-damaged chicken basilar papillae (BP). Analysis of the amplification products indicated the presence of mRNAs for epidermal growth factor receptor (EGFR), fibroblast factor receptor (FGFR), insulin-like growth factor receptor (IGFR), insulin receptor (IR), retinoic acid receptor beta (RAR beta), retinoic acid receptor gamma (RXR gamma), and basic fibroblast growth factor (BFGF) in both normal and noise-damaged BP. The RT-PCR products generated were characterized by size and sequencing analysis to confirm the identities of the target molecules. The subcellular localization of the mature protein analogs for EGFR, FGFR, IGFR, RAR beta, and BFGF were identified using fluorescence immunocytochemistry and confocal laser scanning microscopy. These experiments indicated that EGFR is present in the stereociliary bundles in the hair cells, IGFR is not present in the cells of the BP, BFGF localizes in the nuclei of supporting cells in the BP, but not hair cells or hyaline cells, and that RAR beta localizes in the perinuclear regions of hair cells. The subcellular distributions of these proteins were consistent in both noise-damaged and control BP. FGFR, in contrast, changed its distribution in the tissue after noise damage. In normal BP, FGFR is concentrated in the stereocilia of hair cells. However, in damaged regions of noise-exposed chick cochleae, FGFR is heavily expressed in the expanded apical regions of the supporting cells. These findings suggest that BFGF and retinoic acid may potentially play a role in the mechanisms which regulate the regeneration of chicken cochlear hair cells.
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PMID:Potential role of bFGF and retinoic acid in the regeneration of chicken cochlear hair cells. 878 6

The insulin family of peptides and their receptors influence cellular growth in very early preimplantation embryos. In this study their expression and role in renal organogenesis was investigated. By immunofluorescence microscopy and in situ hybridization, insulin receptor (IR) expression was seen in the ureteric bud branches and early nephron precursors in mouse metanephroi harvested at day 13 of gestation. The expression gradually decreased in successive stages of gestation, and it was confined mainly to renal tubules in 1-week-old mice. Similar developmental regulation of the IR and insulin was observed by reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. Addition of insulin into the culture medium at low concentrations, ranging from 40 to 400 ng/ml, induced trophic changes and increased [3H]thymidine incorporation in the embryonic renal explants, and inclusion of IR beta-subunit-specific antisense oligodeoxynucleotide caused marked dysmorphogenesis and growth retardation of the metanephroi. Specificity of the antisense effect was reflected by immunoprecipitation experiments in which translational blockade of the beta subunit of the IR was observed. RT-PCR analyses revealed that the alpha subunit of the IR was unaffected by the antisense treatment of metanephric explants. Concomitantly, de novo synthesis of morphogenetic regulatory extracellular matrix proteins, especially the proteoglycans, was decreased. Gel-shift analyses indicated a failure in the activation of c-fos promoter region binding protein(s) by insulin in the antisense oligodeoxynucleotide-treated explants. These studies suggest that insulin and its putative receptor are developmentally regulated in the murine embryonic metanephros, and they play a role in renal organogenesis, possibly by affecting other modulators of morphogenesis-i.e., extracellular matrix proteins and protooncogenes.
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PMID:Developmental regulation and the role of insulin and insulin receptor in metanephrogenesis. 919 38

The expression of the ob gene product leptin in adipose tissues has been previously described to be regulated by insulin in vivo and vitro. Akt, a ser/thr kinase with a pleckstrin homology domain, has recently been identified to function in the insulin receptor signaling cascade. The aim of this study was to investigate the role of Akt in the production of leptin by adipocytes. Therefore, we examined leptin production by 3T3-L1 adipocytes stably expressing a myristoylated version of Akt which is constitutively active. Leptin levels in the supernatants of serum starved, nonstimulated 3T3-L1 adipocytes were determined by radioimmunoassay (RIA). Expression of the constitutively active Akt was found to induce a more than 20-fold increase in leptin levels whereas a control non-myristoylated Akt had no effect. Leptin mRNA levels as determined by either RNase protection assay or reverse transcriptase (RT)-polymerase chain reaction (PCR) were not elevated by the constitutively active Akt. These results indicate that Akt can induce leptin production in 3T3-L1 adipocytes via a non-transcriptional mechanism.
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PMID:A constitutively active version of the Ser/Thr kinase Akt induces production of the ob gene product, leptin, in 3T3-L1 adipocytes. 923 12

In mammals, one of the major actions of insulin-like growth factor I (IGF-I) is to increase skeletal growth by stimulating new cartilage formation. IGF-I stimulates chondrocytes in vitro to synthesize new cartilage matrix, measured by enhanced uptake of 35S-sulfate, but the addition of insulin does not produce a similar effect except when added at high concentrations. However, recent studies have shown that, in teleosts, both insulin and IGF-I are potent activators of 35S-sulfate uptake in gill cartilage. To further characterize the growth-promoting activities of these hormones in fish, we have used reverse transcriptase-linked PCR to analyze the expression of insulin receptor family genes in salmon gill cartilage. Partial cDNA sequences encoding the tyrosine kinase domains from six distinct members of the IR gene family were obtained, and sequence comparisons revealed that four of the cDNAs encoded amino acid sequences that were highly homologous to human IR whereas the encoded sequences from two of the cDNAs were more similar to the human type I IGF receptor (IGF-R). Furthermore, a comparative reverse transcriptase-linked PCR assay revealed that the four putative IR mRNAs expressed in toto in gill cartilage were 56% of that found in liver whereas the expressed amount of the two IGF-R mRNAs was 9-fold higher compared with liver. These results suggest that the chondrogenic actions of insulin and IGF-I in fish are mediated by the ligands binding to their cognate receptors. However, further studies will be required to characterize the binding properties and relative contribution of the individual IR and IGF-R genes.
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PMID:Expression of multiple insulin and insulin-like growth factor receptor genes in salmon gill cartilage. 935 69

Alternative splicing of the 36-base pair exon 11 of the human insulin receptor (IR) gene and of the corresponding domain of the rat IR gene results in the synthesis of two IR isoforms with distinct functional characteristics. Altered expression of these IR isoforms has been previously demonstrated in the skeletal muscle of patients with non-insulin-dependent diabetes mellitus (NIDDM); however, this observation was not confirmed by other studies and is still a matter of debate. To assess whether the reported altered isoform expression is due to the secondary metabolic derangement of diabetes, we examined alternative splicing of IR mRNAs (IR36+ and IR36-, corresponding to human Ex11+ and Ex11-) in the skeletal muscle and liver of 6-hour fasting 90% pancreatectomized insulin-resistant diabetic and control Sprague-Dawley rats, using the reverse transcriptase-polymerase chain reaction (PCR) technique. Both diabetic and control rats showed the same pattern of IR mRNA expression: the liver exclusively expressed IR36+ mRNA, whereas only IR36- mRNA was detected in muscle. In conclusion, diabetes mellitus per se does not alter the expression of IR isoforms in the liver and skeletal muscle, and therefore, at least in this animal model of NIDDM, impaired insulin action develops independently from a relative increase in IR36+ mRNA expression in skeletal muscle.
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PMID:Expression of the two insulin receptor isoforms is not altered in the skeletal muscle and liver of diabetic rats. 947 57

Previously we demonstrated that bradykinin infusion could increase glucose uptake into dog peripheral tissues, and that bradykinin could potentiate insulin-induced glucose uptake through glucose transporter 4 (GLUT4) translocation in dog adipocytes. However, skeletal muscle is the predominant tissue for insulin-mediated glucose disposal. The aim of this study was to determine how bradykinin affected insulin-stimulated glucose uptake in dog skeletal muscle and myotubes transformed from rat L6 myoblasts. The bradykinin receptor binding studies revealed that dog skeletal muscle and rat L6 myoblasts possessed significant numbers of bradykinin receptors (Kd = 88 and 76 pmol/l, Bmax = 82.5 and 20 fmol/mg protein respectively). An RT-PCR (reverse transcriptase-polymerase chain reaction) amplification showed mRNA specific for bradykinin B2 receptor in both cells. Bradykinin significantly increased 2-deoxyglucose uptake in isolated muscle and L6 myoblasts in the presence of insulin (10(-7) mol/l) in a dose-dependent manner, but not in the absence of insulin. Bradykinin also enhanced insulin-stimulated GLUT4 translocation, and insulin-induced phosphorylation of insulin receptor beta subunit and insulin receptor substrate-1 (IRS-1) without affecting the binding affinities or numbers of cell surface insulin receptors in both cells. It is concluded that bradykinin could potentiate the insulin-induced glucose uptake through GLUT4 translocation in dog skeletal muscle and rat L6 myoblasts. This effect could be explained by the potency of bradykinin to upregulate the insulin receptor tyrosine kinase activity which stimulates phosphorylation of IRS-1, followed by an increase in GLUT4 translocation.
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PMID:Bradykinin potentiates insulin-stimulated glucose uptake and enhances insulin signal through the bradykinin B2 receptor in dog skeletal muscle and rat L6 myoblasts. 953 11


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