UNIPROT:P01185 - FACTA Search

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Query: UNIPROT:P01185 (vasopressin)
23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulation of pituitary vasopressin V1b receptors plays a critical role in regulating pituitary adrenocorticotropic hormone (ACTH) secretion during adaptation to stress. The objective of this study was to isolate the promoter regulatory region of the V1b receptor gene to better understand the molecular mechanisms involved in V1b receptor regulation. Screening of a rat genomic library using probes directed to the coding region and to the 5'UTR of the rat V1b receptor resulted in the isolation of several clones containing the 5'upstream regions of the V1b receptor cDNA. Sequencing of an 11.2 Kb fragment revealed 8.2 Kb upsteam of the reported cDNA sequence, which contains a putative promoter regulatory region. The 3' end of the clone contained 1472 base pairs corresponding to the recognized cDNA sequence, followed by 1506 bp of unknown sequence located at the end of the sixth transmembrane domain, probably corresponding to an intron, characteristic of these family of receptors. An additional 161 bp intron was found in the 5'UTR, similar to that described in the rat oxytocin receptor gene. 5'RACE and RNase protection analysis mapped two major putative transcription start points at -830 and -861 bp from the starting methionine. Analysis of the putative promoter region showed no indication of a proximal TATA box, but the presence of a CACA box, a GAGA box, several AP-1 and AP-2 sites and a cluster of Sp1 sites upstream of the AP-2 sites. A luciferase construct containing a 2.1-kb of putative promoter, and part of the 5'UTR including the first intron, showed promoter activity when transfected into COS-7, CHO and PC12 cell lines but not in AtT-20 cells. A similar construct without the intron and distal 5'UTR sequence has no promoter activity in the same cell lines. In summary, the V1b receptor gene contains at least 3 exons and 2 introns. The 5'flanking sequence contains several potential sites for transcriptional regulation, and induced luciferace activity only in constructs containing intron 1, suggesting that the latter is important for receptor gene activation. The data provide bases for future analysis of the regulatory elements controlling V1b receptor transcription.
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PMID:Isolation and characterization of the promoter region of the rat vasopressin V1b receptor gene. 1079 83

Different isoforms of the microtubule-associated protein 2 (MAP2) are somatodendritic components of neurons that seem to regulate the stability of the dendritic cytoskeleton. MAP2 localization into dendrites appears to be a complex multicausal mechanism that involves the specific recruitment of MAP2 mRNAs into dendritic compartments. Recently, we have functionally characterized a 640-nucleotide dendritic targeting element (DTE) in the 3' untranslated region (3' UTR) of MAP2 transcripts that mediates extrasomatic mRNA localization in primary neurons (Blichenberg et al. , 1999). In analogy to molecular mechanisms regulating cytoplasmic RNA translocation in other cell systems, we propose that, in vivo, the cis-acting MAP2-DTE interacts with specific protein factors present in neurons. To identify putative trans-acting DTE-binding proteins, we performed in vitro ultraviolet crosslinking assays. Using this experimental system, two 90-kDa and 65-kDa MAP2-RNA trans-acting proteins, MARTA1 and MARTA2, were identified in rat-brain extracts. Both MARTAs bind with high affinity to the MAP2-DTE, but not to other investigated regions of MAP2 transcripts or the somatically restricted alpha-tubulin mRNA. Moreover, MARTA1 and MARTA2 do not bind significantly to other dendritically localized transcripts encoding vasopressin and arg3.1, nor to a dendritic trafficking element from the mRNA encoding the alpha-subunit of the Ca(2+)/calmodulin-dependent protein kinase II. Binding of MARTA1 and MARTA2 to the MAP2-DTE occurs with an affinity in the nanomolar range. Whereas MARTA1 is clearly detectable in crude lysates, cytosolic and ribosomal salt-wash fractions, and in nuclear extracts, MARTA2 is preferentially found in the ribosomal salt-wash preparation. Neither MARTA is restricted to rat brain, and both are present in a number of other rat tissues. Thus, both proteins may be involved in a variety of nuclear and cytoplasmic events that regulate RNA metabolism in different cell types.
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PMID:Two trans-acting rat-brain proteins, MARTA1 and MARTA2, interact specifically with the dendritic targeting element in MAP2 mRNAs. 1092 59

The V(1b) vasopressin receptor, expressed mainly in the corticotroph of the anterior pituitary, mediates the stimulatory effect of vasopressin on ACTH release. To clarify the regulation of receptor expression, we cloned, sequenced (up to approximately 5 kb from the translation start site), and characterized the 5'-flanking region of the rat V(1b) receptor gene. We identified the transcription start site by amplification of cDNA ends and found a new intron within the 5'-untranslated region (5'-UTR) by comparing the sequence with that of cDNA. We then confirmed that the obtained promoter indeed has transcriptional activity by use of the luciferase reporter in AtT-20 mouse corticotroph cells. Interestingly, there were five short upstream open reading frames (uORFs) located within the 5'-UTR that were found to suppress V(1b) expression. Subsequent mutational analyses showed that the two downstream uORFs have an inhibitory effect on expression in both homologous and heterologous contexts. Furthermore, the inhibition did not accompany a parallel decrease in mRNA, suggesting that the suppressive effect occurs at a level downstream of transcription. Taken together, our data strongly suggest that the expression of the V(1b) receptor is regulated at the posttranscriptional as well as transcriptional level through uORFs within the 5'-UTR region of the mRNA. Whether the uORF-mediated regulation of V(1b) expression is functionally linked to any intracellular and/or extracellular factor(s) awaits further research.
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PMID:Involvement of upstream open reading frames in regulation of rat V(1b) vasopressin receptor expression. 1128 61

Hypothalamic corticotropin releasing hormone (CRH) stimulates pituitary ACTH secretion through interaction with type 1 CRH receptors (CRH-R1), the number of which varies during alterations of the hypothalamic-pituitary-adrenal (HPA) axis. CRH-R1 are essential for ACTH responses to stress but CRH receptor content in the pituitary does not correlate with corticotroph responsiveness. This indicates that a small number of receptors is sufficient for full ACTH responses probably through post-receptor interaction with vasopressin (VP) signaling. CRH binding and hybridization studies in adrenalectomized, glucocorticoid-treated or stressed rats revealed divergent levels of CRH receptors and CRH-R1 mRNA in the pituitary, with binding reductions but normal or elevated CRH-R1 mRNA levels during alterations of the HPA axis. Western blot analysis of CRH-R1 protein in pituitary membranes from adrenalectomized rats show unchanged CRH-R1 mRNA levels, but reduced CRH binding associated with significant increases in CRH-R1 protein, suggesting that the decrease in binding is due to homologous desensitization and not to reduced receptor synthesis. In contrast, decreased CRH binding following glucocorticoid administration is associated with reduction in CRH-R1 protein suggesting inhibition of CRH-R1 mRNA translation. Regulation of CRH-R1 translation may involve binding of cytosolic proteins, and a minicistron in the 5'UTR of the CRH-R1 mRNA. Post-transcriptional regulatory mechanisms allowing rapid changes in CRH receptor activity are important for adaptation of corticotroph responsiveness to continuous change in physiological demand.
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PMID:Multiple sites of control of type-1 corticotropin releasing hormone receptor levels in the pituitary. 1193 9

The number of V1b vasopressin receptors (V1bR) in the anterior pituitary plays an important role during adaptation of the hypothalamic-pituitary-adrenal axis to stress in rats. Regulation of V1bR expression involves transcriptional and translational mechanisms. One of the elements mediating transcriptional activation of the rat V1bR gene is a long stretch of GAGA repeats (GAGA box) in the promoter located near the transcription start point capable of binding a protein complex of 127 kDa present in pituitary nuclear extracts. There is a lack of correlation between changes in V1bR mRNA and the number of VP binding sites, suggesting that V1bR expression depends on the efficiency of V1b R mRNA translation into protein. Two mechanisms by which the 5' untranslated region (5'-UTR) of the rat V1bR mRNA can mediate either inhibition or activation of V1bR mRNA translation have been identified. First, upstream open reading frames (ORF) present in the 5'-UTR repress translation of the major ORF encoding the V1b receptor, and secondly, an internal ribosome entry site (IRES) activates V1bR translation. Stimulation of IRES activity through protein kinase C-mediated pathways results in V1bR mRNA translation increasing V1bR protein levels. The existence of multiple loci of regulation for the V1bR at transcriptional and translational levels provides a mechanism to facilitate plasticity of regulation of the number of pituitary vasopressin receptors according to physiological demand.
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PMID:Transcriptional and post-transcriptional mechanisms regulating the rat pituitary vasopressin V1b receptor gene. 1268 34

Posttranscriptional mechanisms play an important role regulating pituitary levels of vasopressin V1b receptors (V1bR) during adaptation to stress. This study investigates the involvement of an internal ribosome entry site (IRES) in the 5'untranslated region (5'UTR) on V1bR translation. Transfection of bicistronic luciferase constructs into MCF-7 cells showed marked increases in translation of the second cistron after insertion of a 499-bp fragment of the V1bR 5'UTR in the intercistronic region, independently of cap-mediated translation, indicating the presence of IRES activity. IRES-mediated translation was potentiated by the protein kinase C activators, 12-O-tetradecanoylphorbol 13-acetate (PMA) and bryostatin 1, and appears to involve phosphorylation of amino terminus of eIF4G. In Chinese hamster ovary cells transfected with pV1bR-green fluorescent protein (pV1bR-GFP), PMA increased V1bR-GFP protein levels when cap-mediated translation was inhibited by rapamycin. The effect of PMA was due to increased translation because it persisted under transcriptional blockade by actinomycin D, and it was completely abolished by cycloheximide. In addition, PMA stimulated [35S]methionine incorporation into V1bR-GFP but not beta-actin in the absence of mRNA changes. The data show that regulation of IRES activity in the 5'UTR of the V1bR mRNA probably through phosphorylation of eIF4G may serve as a mechanism for rapid changes in V1bR translation to meet physiological demands.
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PMID:Translational regulation of the vasopressin v1b receptor involves an internal ribosome entry site. 1286 88

Vasopressin (VP) regulates pituitary corticotroph function by acting upon plasma membrane G-protein receptors of the V1b subtype (V1bR), coupled to calcium-phospholipid signaling. The number of these receptors in the anterior pituitary varies during stress in direct correlation with corticotroph responsiveness, suggesting that the V1bR plays an important role during adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to stress. The molecular regulation of pituitary V1bR involves transcriptional and translational mechanisms. V1bR gene transcription, which is necessary to maintain V1bR mRNA levels, depends on a number of responsive elements in the promoter region, of which the stretch of GA repeats near the transcription start point (GAGA box) is essential. Although transcriptional activation is necessary to maintain V1bR mRNA levels, the lack of correlation between VP binding and V1bR mRNA suggests that V1bR content is mainly regulated at the translational level. Two potential mechanisms by which the 5' untranslated region (5'UTR) of the V1bR mediates negative and positive regulation of V1bR translation were identified. This includes the repressor effect of small open reading frames (ORF) present upstream of the main V1bR ORF, and an internal ribosome entry site (IRES), which activates V1bR translation. The existence of multiple loci of regulation for the V1bR at transcriptional and translational levels provides a mechanism to facilitate plasticity of regulation of the number of pituitary vasopressin receptors according to physiological demand.
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PMID:Regulation of vasopressin V1b receptors and stress adaptation. 1524 Mar 81

We have sequenced a 4.9kb clone (KLB22) which shares 99% sequence homology with the rabbit vasopressin-activated calcium mobilizing (VACM-1) protein. The 5' terminus sequence of KLB22 cDNA (nucleotides 1-1961) is continuous and overlapping with nucleotides 1226-3186 of the VACM-1 cDNA sequence. The 3'UTR of KLB22 cDNA extends beyond the 3'UTR of VACM-1 by 2999nt. KLB22 cDNA encodes a 497 amino acid protein, which putatively begins at Met 284 of the 780 amino acid VACM-1 protein. The in vitro translation of KLB22 cDNA yields a 59kDa protein. When expressed in cos-1 cells, the truncated VACM-1 protein localizes to the nucleus. KLB22 cDNA transfected cells show increased growth rates and increased levels of phosphorylated MAPK when compared to the vector or to VACM-1 cDNA transfected cells. Finally, in vivo, KLB22 protein expression is tissue specific and can be detected in kidney and in heart atrium. These results suggest that truncated VACM-1 cDNA (KLB22) increases cell proliferation through a MAPK pathway.
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PMID:Truncated form of VACM-1/cul-5 with an extended 3' untranslated region stimulates cell growth via a MAPK-dependent pathway. 1658 Oct 22

GATA-4 is a key member of the GATA family of transcription factors involved in cardiac development and growth as well as in cardiac hypertrophy and heart failure. Our previous studies suggest that GATA-4 protein synthesis may be translationally regulated. We report here that the 518-nt long 5'-untranslated region (5'-UTR) of the GATA-4 mRNA, which is predicted to form stable secondary structures (-65 kcal/mol) such as to be inhibitory to cap-dependent initiation, confers efficient translation to monocistronic reporter mRNAs in cell-free extracts. Moreover, uncapped GATA-4 5'-UTR containing monocistronic reporter mRNAs continue to be well translated while capped reporters are insensitive to the inhibition of initiation by cap-analog, suggesting a cap-independent mechanism of initiation. Utilizing a dicistronic luciferase mRNA reporter containing the GATA-4 5'-UTR within the intercistronic region, we demonstrate that this leader sequence confers functional internal ribosome entry site (IRES) activity. The activity of the GATA-4 IRES is unaffected in trans-differentiating P19CL6 cells, however, is strongly stimulated immediately following arginine-vasopressin exposure of H9c2 ventricular myocytes. IRES activity is then maintained at submaximal levels during hypertrophic growth of these cells. Supraphysiological Ca(2+) levels diminished stimulation of IRES activity immediately following exposure to vasopressin and inhibition of protein kinase C activity utilizing a pseudosubstrate peptide sequence blocked IRES activity during hypertrophy. Thus, our data suggest a mechanism for GATA-4 protein synthesis under conditions of reduced global cap-dependent translation, which is maintained at a submaximal level during hypertrophic growth and point to the regulation of GATA-4 IRES activity by sarco(ER)-reticular Ca(2+) stores and PKC.
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PMID:Protein kinase C regulates internal initiation of translation of the GATA-4 mRNA following vasopressin-induced hypertrophy of cardiac myocytes. 1728 39

The 5'-UTR of the vasopressin V1b receptor (V1bR) mRNA contains small open reading frames (ORF) located upstream (u) of the main ORF encoding the V1bR. The ability of the three proximal uORFs to be translated into peptides and their influence on V1bR translation was examined using fusion constructs of uORFs and V5 epitope, or ATG/ATA uORF mutations in the V1bR cDNA. In vitro translation and western blot analysis after transfection of uORF1-V5 or uORF2-V5 into cells revealed that uORF1 can be translated. As predicted by computer analysis, in vitro translation using a rabbit reticulocyte/canine microsome system, immunohistochemistry and western blot in membranes of transfected cells with uORF1-V5 revealed translocation of the uORF1 peptide into membrane fractions. In vitro translation of V1bR cDNA with mutations of the two uORFs proximal to the initiating methionine, uORFs 1 and 2 (Mut 1-2), or uORF2 (Mut 2) showed significantly increased translation of a 46 kDa band corresponding to the V1bR, compared with wild-type (WT) V1bR, an effect that was attenuated by cotranslation of uORF1-V5. Consistently, VP-induced inositol phosphate formation was higher in Chinese hamster ovay cells transfected with Mut 1-2 than with WT V1bR. Immunohistochemical and western blot analysis, using an antibody against uORF1, revealed peptide immunoreactivity in rat pituitary but not in liver. Pituitary uORF immunoreactivity increased following glucocorticoid administration. The present study shows that uORFs in the 5'-UTR of the V1bR mRNA inhibit V1bR translation, and suggests that translation of a 38-amino acid membrane peptide encoded by uORF1 exerts tonic inhibition of V1bR translation.
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PMID:Inhibition of vasopressin V1b receptor translation by upstream open reading frames in the 5'-untranslated region. 1735 21

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