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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To address conflicting reports concerning the number of angiotensin II (AII) receptor type 1 (AT1) coding loci in vertebrates, Southern blot analysis was used to determine the genomic representation of AT1 receptor genes in animals comprising a divergent evolutionary spectrum. The data demonstrate that the AT1 receptor gene is present as a single genomic copy in a broad spectrum of animals including human, monkey, dog, cow, rabbit, and chicken. In contrast, members of the rodent taxonomic order contain two genes in their genomes. These two genes may have arisen in rodents as a consequence of a gene duplication event that occurred during evolution following the branching of rodents from the mammalian phylogenetic tree. In order to investigate the properties of the human AT1 receptor in a pure cell system, the recombinant human AT1 receptor was stably expressed in mouse L cells. An isolated cell line, designated LhAT1-D6, was found to express abundant levels of recombinant receptor [430 +/- 15 fmol/mg] exhibiting high affinity [KD = 0.15 +/- 0.02 nM] for [125I][SAR1, Ile8] angiotensin II (SIA). The pharmacological profile of ligands competing for [125I] SIA binding to the expressed receptor was in accordance with that of the natural receptor. Radioligand binding of the expressed receptor was decreased in the presence of the non-hydrolyzable analog of GTP, guanosine 5'-(gamma-thio) triphosphate [GTP gamma S]. Angiotensin II evoked a rapid efflux of 45Ca2+ from LhAT1-D6 cells that was blocked by AT1 receptor specific antagonists. In addition, AII inhibited forskolin-stimulated cAMP accumulation in these cells which was blocked by the AT-1 antagonist. Thus, the LhAT1-D6 cell line provides a powerful tool to explore the human AT1 receptor regulation.
Mol Cell Biochem 1994 Feb 09
PMID:Human AT1 receptor is a single copy gene: characterization in a stable cell line. 804 68

Cytosolic activities in liver, stomach, small intestine, colon, lung, kidney, brain and spleen of hamster have been shown to be capable of N-acetylation, O-acetylation and N,O-acetyltransfer utilizing aromatic amine derivatives as substrates. These activities, which have been implicated in the metabolic activation and carcinogenicity of these compounds, were highest in the liver and small intestine. N-Acetylation could be demonstrated with either acetyl CoA or N-hydroxy-N-acetylaminoarenes serving as acetyl donors. Each of these tissues gave two immunoreactive bands (approximately 29 and 31 kDa) on Western blots using anti-rat AT monoclonal antibodies for detection. Single copies of two distinct acetyltransferase genes, designated AT1 and AT2, were detected in hamster DNA by Southern blot analysis using gene-specific hybridization probes for the 3' end of the AT coding regions. A third gene with > 80% sequence similarity to codons 118-158 of AT2 was also detected. Sequence analysis of the two AT genes showed that both had intronless, 0.87 kb coding regions. One was identical with the AT1 reported by Abu-Zeid et al. (Abu-Zeid,M., Nagata, K., Miyata,M., Ozawa,S., Fukuhara,M. and Yamazoe,Y., 1991, An arylamine acetyltransferase (AT-1) from Syrian golden hamster liver: cloning, complete nucleotide sequence, and expression in mammalian cells. Mol. Carcinogen., 4, 81-88). The second, AT2 (GenBank accession number L24912), coded for a 290 amino acid sequence that was 79% homologous with hamster AT1 and had a calculated molecular weight of 33.8 kDa, a theoretical pI of 5.96 and the three cysteines that have been conserved in all known vertebrate ATs at positions 44, 68 and 223. Northern blot hybridization using gene-specific AT probes detected mRNAs for both AT1 and AT2 in each of the eight tissues analyzed. Two AT1 transcripts, approximately 1.7 and 2.3 kb, were found in approximately equal ratios in all eight tissues. Three transcripts for AT2, approximately 1.9, 2.1 and 2.4 kb, were present in approximately equal ratios in the brain, small intestine, lung and colon. The liver, stomach, kidney and spleen had primarily the smaller two AT2 mRNAs. The overall abundance of AT mRNAs was highest in liver, small intestine and colon. The coding sequences of all AT mRNAs analyzed were identical to their corresponding genes, although the lengths of both the 5' and 3' untranslated transcript regions varied.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Biochemical and genetic analysis of two acetyltransferases from hamster tissues that can metabolize aromatic amine derivatives. 805 37

The relative binding affinities of non-peptide antagonists, and the sensitivity of 125I-angiotensin II (125I-AII) binding to the reducing agent, dithiothreitol, indicated the presence of AT1 angiotensin receptors on RIE-1 rat intestinal epithelial cells. Consistent with this finding, AT1 angiotensin receptor mRNA was detected in RIE-1 cells using Northern blotting, whereas no mas transcripts (which also encode an angiotensin receptor) were detectable using a RNAse protection assay. At 37 degrees C, 125I-AII rapidly bound to RIE-1 cells and internalised into an acid-inaccessible compartment, which resulted in the depletion of 125I-AII from the binding medium. Following overnight incubation of RIE-1 cells with 125I-AII at 4 degrees C, the majority of bound ligand was also, unexpectedly, found to be inaccessible to subsequent acid elution. After warming these cultures to 37 degrees C, acid-inaccessible 125I-radioactivity rapidly disappeared from the cells, and 125I-labelled degradation products accumulated in the medium. Scatchard analysis of the concentration-dependent binding of 125I-AII solely to the acid-accessible sites on RIE-1 cells revealed little difference to the KD value obtained from total 125I-AII binding (to both acid-accessible and -inaccessible sites), but only approximately 15% of the number of sites.
Biochem Mol Biol Int 1994 Apr
PMID:Characterisation of AT1 angiotensin receptors on cultured rat intestinal epithelial (RIE-1) cells. 806 42

The vasoactive peptides endothelin-1 (ET-1) and angiotensin-II (AII) have been implicated in chronic hypertension and may play important roles in related vascular diseases such as restenosis and atherosclerosis. Using a rat aortic smooth muscle (RASM) cell model, both ET-1 and AII induced concentration-dependent delayed increases in DNA synthesis relative to that in the serum-deprived controls. Stimulation of DNA synthesis was maximal at 100 nM for each peptide. All treatment of RASM cells resulted in a greater mitogenic effect (4- to 7-fold) than that observed for ET-1 (3-fold). When added in the presence of AII, ET-1 had a supplemental effect on DNA synthesis (5- to 10-fold above control). Although RASM cells expressed both ETA and AT1 receptors, radioligand binding experiments indicated that approximately 10-fold as many AT1 receptors as ETA receptors were present. In signal transduction studies, ET-1 and AII each elicited concentration-dependent increases in the intracellular Ca2+ concentration. ET-1 and AII also stimulated phosphoinositide metabolism and phosphorylation of a specific substrate for protein kinase-C. The release of total inositol phosphates in response to ET-1 and AII was concentration dependent and inhibited by the ETA receptor-selective antagonist BQ-123 and the AT1 receptor-selective antagonist losartan, respectively. In addition, tyrosine phosphorylation of 120- and 75-kilodalton proteins as well as the mitogen-activated protein kinases p44mapk and p42mapk was observed within 5 min of the addition of either ET-1 or AII. Taken together, these data indicate that ET-1 and AII may promote smooth muscle cell growth through common intracellular signaling mechanisms.
Mol Endocrinol 1994 Feb
PMID:Endothelin-1 and angiotensin-II stimulate delayed mitogenesis in cultured rat aortic smooth muscle cells: evidence for common signaling mechanisms. 817 Apr 71

We have recently described the appearance of a specific DNA-binding protein in nuclei from human cells exposed to ionizing radiation which was not detected in nuclear extracts from unperturbed cells (Singh, S. P., and Lavin, M. F. (1990) Mol. Cell. Biol. 10, 5279-5285). We report here a similar activity which is constitutively present in nuclei of both unirradiated and irradiated cells from patients with the human genetic disorder ataxia telangiectasia (A-T). Activity was present in unirradiated nuclear extracts from 3 A-T cell lines of different complementation groups, but was not detected or was present only at a low level in 4 controls. Active protein was detected in the cytoplasm of both cell types. Exposure to ionizing radiation did not change the amount of DNA binding activity in A-T nuclei but led to an increase in nuclei from 4 control cell lines. Purification of the binding activities from A-T nuclei and control cytoplasm was carried out by affinity chromatography, as described previously for control extracts (Teale, B., Singh, S. P., Khanna, K. K., Findik, D., and Lavin, M. F. (1992) J. Biol. Chem. 267, 10295-10301). Southwestern analysis and UV cross-linking confirmed the presence of a major DNA-binding species at 70 kDa in both cases with a minor binding activity at 47 kDa also evident. It was not possible to distinguish between the binding activities from A-T and control cells under different conditions, and phosphorylation was required for binding activity in both cases. Footprint analysis revealed that the same sequence was being recognized by the control and A-T proteins. The constitutive presence of a specific radiation-responsive DNA-binding protein in A-T cells may be indicative of a continuous state of stress in these cells.
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PMID:Radiation-activated DNA-binding protein constitutively present in ataxia telangiectasia nuclei. 822 53

The angiotensin II (Ang II)-binding sites in rat adrenal gland membranes were characterized using 125I-radiolabelled Ang II. While Scatchard analysis identified a single population of Ang II receptor sites, isoelectric focusing (IEF) on polyacrylamide gels revealed four peaks of specific Ang II binding which migrated to isoelectric points (pI values) 6.8, 6.7, 6.5 and 6.3. In binding assays in the presence of an excess of the Ang II receptor AT1 subtype antagonist DuP 753, a monophasic dose-dependent displacement of 125I-labelled Ang II binding by the Ang II receptor AT2 subtype antagonist CGP42112A was observed, and vice versa. In this system, reduction of disulphide bridges using 1 mmol dithiothreitol (DTT)/l markedly increased the number of binding sites in the adrenal zona glomerulosa without affecting receptor affinity. Using IEF, it was found that both DuP 753 and CGP42112A were able to reduce specific binding of each of the four peaks to some extent. However, the predominant effect of DuP 753 was to reduce the labelling of the isoform at pI 6.7 substantially, while CGP42112A significantly inhibited the specific 125I-labelled Ang II binding to the pI 6.3 isoform. When DuP 753 and CGP42112A were used together, specific binding of 125I-labelled Ang II to the isoforms of pI values 6.8, 6.7 and 6.3 was completely eliminated. These data suggest that the four peaks of specific binding found may be composed of different isoforms of both AT1 and AT2 receptor subtypes and that the Ang II receptor isoforms which migrated to pI 6.7 and pI 6.3 are predominantly composed of AT1 and AT2 receptor subtypes respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Endocrinol 1993 Aug
PMID:Angiotensin II receptor isoforms in the rat adrenal gland: studies with the selective subtype antagonists DuP 753 and CGP42112A. 824 Jun 73

Replication protein A (RPA), the trimeric single-stranded DNA-binding protein complex of eukaryotic cells, is important to DNA replication and repair. Phosphorylation of the p34 subunit of RPA is modulated by the cell cycle, occurring during S and G2 but not during G1. The function of phosphorylated p34 remains unknown. We show that RPA p34 phosphorylation is significantly induced by ionizing radiation. The phosphorylated form, p36, is similar if not identical to the phosphorylated S/G2 form. gamma-Irradiation-induced phosphorylation occurs without new protein synthesis and in cells in G1. Mutation of cdc2-type protein kinase phosphorylation sites in p34 eliminates the ionizing radiation response. The gamma-irradiation-induced phosphorylation of RPA p34 is delayed in cells from ataxia telangiectasia, a human inherited disease conferring DNA repair defects and early-onset tumorigenesis. UV-induced phosphorylation of RPA p34 occurs less rapidly than gamma-irradiation-induced phosphorylation but is kinetically similar between ataxia telangiectasia and normal cells. This is the first time that modification of a repair protein, RPA, has been linked with a DNA damage response and suggests that phosphorylation may play a role in regulating DNA repair pathways.
Mol Cell Biol 1993 Dec
PMID:The ionizing radiation-induced replication protein A phosphorylation response differs between ataxia telangiectasia and normal human cells. 824 44

The distribution and function of AII receptor subtypes was evaluated in different preparations of rat hearts. Autoradiographic experiments and binding experiments on isolated membranes showed a large expression of [125I]Sar1,Ile8-AII binding sites in the atria of neonatal Wistar Kyoto rats which were predominantly of the AT2 subtype. Atrial and ventricular cells, isolated from neonatal rat hearts and maintained for 3 days in culture demonstrated primarily AT1 binding sites. Stimulation of cultured atrial cells with AII resulted in an increase in inositol phosphate turnover and in intracellular calcium. The latter action was completely abolished by Losartan. Finally, in atria isolated from 2-month-old rats, AII produced a 17-19% increase in contractile force that was completely abolished by Losartan but not by PD 123319, thus indicating the presence of functional AT1 receptors.
J Mol Cell Cardiol 1993 Nov
PMID:Angiotensin II receptor subtypes and biological responses in the rat heart. 830 69

A 2046-base pair cDNA clone, homologous to mammalian angiotensin (AT) AT1 receptors, was isolated from a library prepared from adrenal glands of the domestic turkey (Meleagris gallopavo). Sequence analysis of the cDNA insert in clone pTAT2' reveals a 1077-base pair open reading frame predicting a 359-amino acid protein approximately 75% homologous to mammalian AT1 receptors. Saturation radioligand binding studies performed in membranes of COS-7 cells transfected with pTAT2' show high affinity specific binding of 125I-angiotensin II, with a Kd of 172 pM. The rank order of affinities for a series of ligands determined by competition binding studies is angiotensin II > or = [Sar1,Ile8]-angiotensin II > angiotensin III approximately [Sar1,Ala8]-angiotensin II approximately CGP42112A > angiotensin I > Dup753 > PD123177. This rank order of affinity series differs substantially from that for mammalian AT1 receptors and AT2 binding sites. Angiotensin II (100 nM) can stimulate inositol phosphate production similarly in COS-7 cells transfected with pTAT2' and in COS-7 cells transfected with the AT1a receptor cDNA pCa18b. This response in pTAT2'-transfected cells is not attenuated in the presence of 30 microM Dup753. In contrast, this concentration of antagonist attenuates > 90% of the inositol phosphate response to angiotensin II in COS-7 cells transfected with the rat AT1a receptor cDNA. These results demonstrate an avian structural homologue of mammalian AT1 receptors possessing distinct pharmacological properties with both peptide and nonpeptide AT receptor ligands.
Mol Pharmacol 1993 Jul
PMID:A cloned angiotensin receptor isoform from the turkey adrenal gland is pharmacologically distinct from mammalian angiotensin receptors. 834 Dec 66

The high resolution mapping of the ataxia telangiectasia (A-T) locus on chromosome 11q22-23 requires the generation of new polymorphic markers specifically within the segment of 11q22-23 to which the locus has been assigned. We have made use of a library of Alu-PCR clones, amplified from a radiation reduced somatic cell hybrid containing the relevant chromosome 11 segment, to generate sequence tagged sites (STS) within the 11q22-23 region and have used YAC clones to extend the loci identified by these STSs. The identification of paired polymorphisms (from Alu-PCR and the associated YAC derived clone), which are physically linked, but which show minimal linkage disequilibrium, provides a highly informative haplotype for use in genetic linkage analysis in A-T families. We describe the characterisation of 2 such polymorphic loci, D11S535 and D11S611, which map between existing flanking markers, and which provide additional information on the location of the major A-T locus.
Hum Mol Genet 1993 Jul
PMID:Paired STSs amplified from radiation hybrids, and from associated YACs, identify highly polymorphic loci flanking the ataxia telangiectasia locus on chromosome 11q22-23. 836 79


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