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

In isolated rat hepatocytes PMA, angiotensin II and to a lesser extent other hormones induce an early genetic response (increased expression of c-fos, c-mos, c-myc and beta-actin) without altering the expression of the glyceraldehyde 3-phosphate dehydrogenase gene. PMA, PDB and O-met-PMA, but not alpha-phorbol, stimulated c-fos expression. The effect of angiotensin II was inhibited by the AT1 antagonist, Losartan (DuP 753) (Ki approx. 25 nM), but not by the AT2 antagonist PD123177. Angiotensin II was much more effective than vasopressin or epinephrine in inducing proto-oncogene expression which suggests that angiotensin II receptors may exert actions in addition to those shared with the receptors for the other calcium-mobilizing hormones. The effect of PMA and angiotensin II on c-fos expression took place rapidly, with half times of 7 and 12 min, respectively. Actinomycin D markedly diminished basal c-fos expression whereas cycloheximide had the opposite effect. Actinomycin D diminished the effect of PMA and angiotensin II but it did not block them. PMA and the calcium-mobilizing hormones increased c-fos expression above the level observed with cycloheximide alone. These data suggest that PMA and the calcium-mobilizing hormones increased both transcription of the c-fos gene and stabilization of the proto-oncogene mRNA.
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PMID:Angiotensin II and active phorbol esters induce proto-oncogene expression in isolated rat hepatocytes. 152 Jul 5

Quiescent cultures of Swiss 3T3 cells can be stimulated to recommence DNA synthesis by polypeptide growth factors, neuropeptides, and various pharmacologic agents that act via multiple signal transduction pathways. Neuropeptides of the bombesin family provide potent mitogens to elucidate these pathways. These peptides bind to specific receptors that have been characterized by radioligand binding and sensitivity to antagonists and identified as glycoproteins with a Mr of 75,000-85,000 by chemical cross-linking. After binding, bombesin elicits a cascade of early molecular events including stimulation of phosphorylation of the acidic Mr 80,000 cellular protein, which is a major substrate of protein kinase C; Ca2+ mobilization mediated by Ins(1,4,5)P3, Na+ and K+ fluxes, transmodulation of EGF receptor, enhancement of cAMP accumulation, and expression of the proto-oncogenes c-fos and c-myc. Studies using membrane preparations and permeabilized 3T3 cells indicate that G proteins play a role in the transduction of the mitogenic signal triggered by the binding of bombesin to its receptor. A pertussis toxin-insensitive G protein couples the bombesin receptor to the generation of a signal that activates protein kinase C, whereas a pertussis toxin-sensitive G protein mediates cross-talk between transmembrane signaling pathways. Bombesin-mediated mitogenesis can be blocked by different antagonists and by interrupting the signal-transduction process at various postreceptor levels. Thus, prolonged treatment with vasopressin causes heterologous desensitization to the mitogenic action of bombesin. This mitogenic block is mediated by uncoupling the receptor from its signaling system. Loss of responsiveness to bombesin-stimulated DNA synthesis is also induced by down-regulation of protein kinase C.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bombesin stimulation of mitogenesis. Specific receptors, signal transduction, and early events. 217 58

The expression of two oncogenes (conc) c-myc and c-fos, coding for nuclear proteins which play a regulatory role in growth and differentiation, and of two genes coding for two heat shock proteins (HSP) 68 (molecular weight 68,000) and 70 (molecular weight 70,000), which have a protective function during stress, have been investigated by Northern blot analysis of the total RNA, extracted from adult rat ventricle and aorta. (1) The two onc transcripts are absent from these tissues but their expression can be enhanced by a pretreatment with cycloheximide. (2) The HSP70 is, in part, constitutive, while HSP68 is not; both are thermo-inducible in an isolated coronary perfused rat heart. (3) The four messenger RNA (mRNA) are expressed in both ventricles and aorta, 1 or 2 hours after i.p. injection of 6 mg/kg phenylephrine or 12 IU/kg of vasopressin. (4) They are also induced by a continuous or discontinuous injection of angiotensin II (7.5 micrograms/kg per min) for 1-2 h, but only in the aorta. The lack of ventricular response to angiotensin II in rat ventricles has been attributed to the lack of angiotensin II receptors in this tissue. This indicates that, in addition to mechanical factors, circulating hormones which have in common the use of the phosphoinositol pathway, may activate the expression of genes coding for regulatory proteins. This may play a role in the genesis of both ventricular and aortic hypertrophy.
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PMID:Phenylephrine, vasopressin and angiotensin II as determinants of proto-oncogene and heat-shock protein gene expression in adult rat heart and aorta. 270 15

The role of the phosphoinositide turnover-protein kinase C pathway in mediating PDGF-stimulated c-myc expression and cell proliferation was studied. Both direct activators of kinase C (e.g. phorbol ester analogues) and hormones that activate kinase C via receptor-mediated phosphoinositide turnover (e.g. PDGF, bradykinin, or vasopressin) elicited a rapid increase in c-myc mRNA expression. Desensitization of the kinase C pathway by prolonged exposure to phorbol abolished the induction of c-myc by subsequent phorbol challenge and attenuated c-myc induction by PDGF and bradykinin, but did not affect PDGF-stimulated mitogenesis. Bradykinin and phorbol esters stimulated the same magnitude of c-myc expression as PDGF but elicited less than one-tenth the PDGF-induced mitogenic response. We conclude that stimulation of c-myc expression is a common response to a diverse group of agents that elicit phosphoinositide turnover and activate protein kinase C, and that neither activation of protein kinase C nor enhanced c-myc expression is sufficient for the mitogenic action of PDGF.
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PMID:c-myc gene expression is stimulated by agents that activate protein kinase C and does not account for the mitogenic effect of PDGF. 300 Jun 1

Glucose depressed DNA synthesis in rat hepatocytes in primary culture. As compared to controls cultured with 5.6 mM glucose, maximal (> or = 75%) inhibition was obtained at 20-30 mM, and half-maximal effect at 10-15 mM. Comparison of D- and L-glucose showed that the effect was specific for the D-form. Maximal inhibition required the presence of glucose during the first 24 hours of culture. The expression of the c-myc gene was reduced when the hepatocytes were cultured in the presence of elevated glucose. The responses to epidermal growth factor, insulin and vasopressin, in terms of percentual stimulation of DNA synthesis, were qualitatively similar at 5.6 and 16.8 mM glucose, while glucagon stimulated more strongly when the glucose concentration was increased; glucagon at concentrations > or = 1 nM reversed the inhibition by glucose. 8-Br-cAMP mimicked the effect of glucagon. These results suggest that an increase in the level of glucose depresses hepatocyte DNA synthesis. The effect is associated with lowered expression of the c-myc gene and is counteracted by cAMP.
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PMID:Elevated glucose concentrations inhibit DNA synthesis and expression of c-myc in cultured hepatocytes. 806 Mar 30

Vasopressin-dependent membrane insertion of aquaporin-2 (AQP-2) in collecting duct principal cells has been demonstrated in vivo and in vitro. However, the hypothesis that the AQP-2 molecule recycles between intracellular vesicles and the plasma membrane in response to hormonal stimulation and withdrawal remains to be demonstrated directly. In the present study, we examined AQP-2 recycling between intracellular vesicles and the plasma membrane in the absence of de novo protein synthesis using LLC-PK1 cells transfected with an AQP-2-c-myc construct. Cells were treated with cycloheximide for 30 min prior to vasopressin stimulation, and all subsequent treatments were performed in the continued presence of cycloheximide. Complete inhibition of AQP-2 biosynthesis by cycloheximide was verified by immuno-precipitation. Immunofluorescence revealed that AQP-2 was located on intracellular vesicles in nonstimulated cells but was relocated to the plasma membrane after vasopressin treatment, even in the presence of cycloheximide. After vasopressin washout, AQP-2 was retrieved to intracellular vesicles and was relocated to the plasma membrane after restimulation with forskolin. Subsequent forskolin washout resulted in AQP-2 endocytosis, and a second stimulation with forskolin resulted in relocation to the plasma membrane. These data, obtained in the absence of de novo protein synthesis, clearly indicate that AQP-2 can be recycled multiple times between intracellular vesicles and the plasma membrane.
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PMID:Direct demonstration of aquaporin-2 water channel recycling in stably transfected LLC-PK1 epithelial cells. 878 Feb 59

We characterized truncations of the human vasopressin V2 receptor to determine the role of the intracellular C-terminus (comprising about 44 amino acids) in receptor function and cell surface expression. In contrast to the wild-type receptor, the naturally occurring mutant R337X failed to confer specific [3H]AVP binding to transfected cells. In addition, no vasopressin-sensitive adenylyl cyclase was detectable in membrane preparations of these cells. Laser scanning microscopy revealed that c-myc epitope- or green fluorescent protein-tagged R337X mutant receptors were retained within the endoplasmic reticulum. Increasing the number of C-terminal residues (truncations after codons 348, 354 and 356) restored G protein coupling, but revealed a length-dependent reduction of cell surface expression. Replacement of positively charged residues within the C-terminus by glutamine residues also decreased cell surface expression. A chimeric V2 receptor with the C-terminus replaced by that of the beta2-adrenergic receptor did not bind [3H]AVP and was retained within the cell. These data suggest that residues in the N-terminal part of the C-terminus are necessary for correct folding and that C-terminal residues are important for efficient cell surface expression.
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PMID:Folding and cell surface expression of the vasopressin V2 receptor: requirement of the intracellular C-terminus. 953 15

Before the identification of aquaporin (AQP) proteins, vasopressin-regulated "water channels" were identified by freeze-fracture electron microscopy as aggregates or clusters of intramembraneous particles (IMPs) on hormonally stimulated target cell membranes. In the kidney collecting duct, these IMP clusters were subsequently identified as possible sites of clathrin-coated pit formation on the plasma membrane, and a clathrin-mediated mechanism for internalization of vasopressin-sensitive water channels was suggested. Using an antibody raised against the extracellular C loop of AQP2, we now provide direct evidence that AQP2 is concentrated in clathrin-coated pits on the apical surface of collecting duct principal cells. Furthermore, by using a fracture-label technique applied to LLC-PK(1) cells expressing an AQP2-c-myc construct, we show that AQP2 is located in IMP aggregates and is concentrated in shallow membrane invaginations on the surface of forskolin-stimulated cells. We also studied the functional role of clathrin-coated pits in AQP2 trafficking by using a GTPase-deficient dynamin mutation (K44A) to inhibit clathrin-mediated endocytosis. Immunofluorescence labeling and freeze-fracture electron microscopy showed that dominant-negative dynamin 1 and dynamin 2 mutants prevent the release of clathrin-coated pits from the plasma membrane and induce an accumulation of AQP2 on the plasma membrane of AQP2-transfected cells. These data provide the first direct evidence that AQP2 is located in clathrin-coated pits and show that AQP2 recycles between the plasma membrane and intracellular vesicles via a dynamin-dependent endocytotic pathway. We propose that the IMP clusters previously associated with vasopressin action represent sites of dynamin-dependent, clathrin-mediated endocytosis in which AQP2 is concentrated before internalization.
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PMID:Aquaporin-2 localization in clathrin-coated pits: inhibition of endocytosis by dominant-negative dynamin. 1199 16

Several agonists acting on G protein-coupled receptors (GPCR) enhance the mitogenic effect of epidermal growth factor (EGF) in rat hepatocytes, through mechanisms that have only partially been clarified. Results in various cells have led to the idea that a major mechanism for GPCR-mediated stimulation of cell growth is transactivation of receptor tyrosine kinases, particularly the EGF receptor (EGFR), leading to rapid phosphorylation of the EGFR and activation of downstream signaling pathways. In the present study cultured rat hepatocytes were exposed to various GPCR agonists, including vasopressin, angiotensin II (Ang.II), norepinephrine, or prostaglandin F(2 alpha) (PGF(2 alpha)). None of these agents increased the phosphorylation of the EGFR or the docking protein Shc. Furthermore, we examined the effect of the GPCR agonists on the expression of two early response genes believed to be involved in growth activation. The GPCR agonists increased the mRNA expression of c-myc, and also of activating transcription factor 3 (ATF3)/liver regeneration factor-1 (LRF-1), which is a novel finding. Finally, the selective EGFR inhibitor AG1478 did not suppress the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) or the induction of c-myc or ATF3/LRF-1 by the GPCR agonists, and did not prevent the comitogenic effects induced by these agents, while it blocked the effect of EGF on these responses. The results suggest that GPCR agonists induce expression of ATF3/LRF-1 and c-myc and exert comitogenic effects through mechanisms that do not require EGFR transactivation.
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PMID:G protein-coupled receptor agonist-stimulated expression of ATF3/LRF-1 and c-myc and comitogenic effects in hepatocytes do not require EGF receptor transactivation. 1538 57

Arginine-vasopressin (AVP) stimulates Na(+) transport and Na-K-ATPase activity via cAMP-dependent PKA activation in the renal cortical collecting duct (CCD). We investigated the role of the Na-K-ATPase in the AVP-induced stimulation of transepithelial Na(+) transport using the mpkCCD(c14) cell model of mammalian collecting duct principal cells. AVP (10(-9) M) stimulated both the amiloride-sensitive transepithelial Na(+) transport measured in intact cells and the maximal Na pump current measured by the ouabain-sensitive short-circuit current in apically permeabilized cells. These effects were associated with increased Na-K-ATPase cell surface expression, measured by Western blotting after streptavidin precipitation of biotinylated cell surface proteins. The effects of AVP on Na pump current and Na-K-ATPase cell surface expression were dependent on PKA activity but independent of increased apical Na(+) entry. Time course experiments revealed that in response to AVP, the cell surface expression of both endogenous Na-K-ATPase and hybrid Na pumps containing a c-myc-tagged wild-type human alpha(1)-subunit increased transiently. Na-K-ATPase cell surface expression was maximal after 30 min and then declined toward baseline after 60 min. Immunoprecipitation experiments showed that PKA activation did not alter total phosphorylation levels of the endogenous Na-K-ATPase alpha-subunit. In addition, mutation of the PKA phosphorylation site (S943A or S943D) did not alter the time course of increased cell surface expression of c-myc-tagged Na-K-ATPase in response to AVP or to dibutyryl-cAMP. Therefore, stimulation of Na-K-ATPase cell surface expression by AVP is dependent on PKA but does not rely on alpha(1)-subunit phosphorylation on serine 943 in the collecting duct principal cells.
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PMID:Stimulation of Na+ transport by AVP is independent of PKA phosphorylation of the Na-K-ATPase in collecting duct principal cells. 1597 90


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