Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inositol trisphosphate receptor (IP3R) in brain has been shown to be a substrate for several different protein kinases in vitro. We have studied the phosphorylation of the IP3R in intact cells by using isolated hepatocytes and an antibody to immunoprecipitate the receptor protein from detergent extracts. Stimulation of 32P-labeled hepatocytes with glucagon or N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (db-cAMP) markedly increased phosphorylation of the IP3R. However, no increase was observed in response to angiotensin II, vasopressin, 12-O-tetradecanoyl-phorbol-13-acetate, or epidermal growth factor. The kinetics of phosphorylation in response to glucagon was both rapid and transient. In agreement with previous studies, physiological concentrations of Ca2+ stimulated D-myo-inositol 1,4,5-trisphosphate (IP3) binding to permeabilized hepatocytes (Pietri, F., Hilly, M., and Mauger, J.-P. (1990) J. Biol. Chem. 265, 17478-17485). Pretreatment of cells with db-cAMP had no effect on binding in the absence of added Ca2+ but enhanced binding measured in the presence of basal low concentrations (0.16-0.25 microM) of Ca2+ and decreased the concentration of Ca2+ required for half-maximal stimulation. The effect of db-cAMP was associated with an increase in affinity of the IP3 binding site without a change in maximum number of binding sites. Preincubation of intact hepatocytes with okadaic acid alone produced an increase in basal phosphorylation of the IP3R, and maximal phosphorylation of the receptor was observed in the presence of both okadaic acid and db-cAMP. However, okadaic acid blocked the effect of db-cAMP and inhibited the effect of Ca2+ on IP3 binding. Detergent-solubilized binding sites were already fully activated and insensitive to modulation by Ca2+ or cAMP-dependent protein kinase. It is proposed that the receptor in native membranes is inhibited and that Ca2+ and cAMP-dependent protein kinase may act to relieve this inhibition.
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PMID:Phosphorylation of the inositol trisphosphate receptor in isolated rat hepatocytes. 822 22

Chronic stimulation of WB rat liver epithelial cells by angiotensin II (Ang II) resulted in the down-regulation of both type I and type III myo-inositol 1,4,5-trisphosphate receptors (IP3Rs). Stimulation with vasopressin, bradykinin, epidermal growth factor, or 12-O-tetradecanoylphorbol-13-acetate was without effect. Ang II-induced down-regulation of IP3Rs could be detected within 2 h and resulted in an inhibition of IP3-induced Ca2+ release from permeabilized cells. IP3R down-regulation was reversible, and both homo- and heterooligomers of IP3Rs were equally susceptible to Ang II-induced degradation. Chloroquine and NH4Cl increased the basal levels of IP3Rs by 2-fold, suggesting that the basal turnover of IP3Rs occurs via a lysosomal pathway. However, Ang II-induced degradation of IP3R was not affected by these inhibitors, suggesting that stimulated degradation of IP3Rs occurs via a non-lysosomal pathway. The cysteine protease and proteasomal inhibitor N-acetyl-Leu-Leu-norleucinal completely prevented Ang II-mediated down-regulation of IP3Rs, whereas the structural analog N-acetyl-Leu-Leu-methioninal was without effect. Lactacystin, a highly specific proteasome inhibitor, also blocked Ang II-mediated IP3R degradation. Stimulation with Ang II increased the amount of IP3R immunoprecipitated by anti-ubiquitin antibodies. We conclude that Ang II-stimulated IP3R degradation involves enhanced ubiquitination of the protein and degradation by the proteasome pathway.
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PMID:Angiotensin II-induced down-regulation of inositol trisphosphate receptors in WB rat liver epithelial cells. Evidence for involvement of the proteasome pathway. 913 93

Sigma-1 receptor (sigma-1R) agonists enhance inositol 1,4,5-trisphosphate (IP3)-dependent calcium release from endoplasmic reticulum by inducing dissociation of ankyrin B 220 (ANK 220) from the IP3 receptor (IP3R-3), releasing it from inhibition. MCF-7 breast tumor cells express little or no sigma-1R and were used here to investigate the effect of receptor overexpression and the role of its N- and C-terminal segments in function. We stably expressed intact sigma-1R (amino acids (aa) 1-223; lines 11 and 41), N-fragment (aa 1-100; line K3), or C-fragment (aa 102-223; line sg101). C-fragment expressed as a peripheral membrane-bound protein that was removable from the endoplasmic reticulum membrane by chaotropic salt wash, consistent with lack of a putative transmembrane domain. The expressed sigma-1R, N-fragment, and C-fragment exhibited normal, low affinity, and no [3H](+)-pentazocine binding activity, respectively. All transfected lines showed constitutive enhancement of bradykinin (BDK)-induced calcium release, because of a decrease in BDK ED50 values. Interestingly, sigma-1R and C-fragment had high activities, whereas the N-fragment was much less active. The antagonist BD1063 behaved as an inverse agonist in sigma-1R cells, whereas C-fragment was insensitive to ligand regulation. Like BDK, vasopressin- and ATP-induced calcium release was enhanced with the same pattern in cell lines. Anti-IP3R-3 immunoprecipitates from cells expressing sigma-1R or C-fragment contained significantly less ANK 220 compared with untransfected or N-fragment cells, indicating a higher amount of ankyrin-free IP3R-3. Anti-ankyrin B immunoprecipitates contained sigma-1R or C-fragment, with markedly lower levels of N-fragment present. These results suggest that sigma-1R overexpression drives sigma agonist-independent dissociation of ANK 220 from IP3R-3, resulting in activation. The C-terminal segment plays a key role in the interaction.
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PMID:Role of sigma-1 receptor C-terminal segment in inositol 1,4,5-trisphosphate receptor activation: constitutive enhancement of calcium signaling in MCF-7 tumor cells. 1853 93