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)

Soluble extracts prepared from quiescent Swiss mouse 3T3 cells that had been briefly exposed to various mitogens exhibited a 2- to 3-fold elevation in phosphorylating activities toward ribosomal protein S6 and a synthetic peptide, Arg-Arg-Leu-Ser-Ser-Leu-Arg-Ala (RRLSSLRA), patterned after a phosphorylation site sequence from S6. Optimal activation of the phosphorylating activity occurred within 15-20 min of exposure of the cells to platelet-derived growth factor (10 ng/ml), epidermal growth factor (100 nM), and insulin (100 nM), and 2-5 min after 12-O-tetradecanoylphorbol-13-acetate (TPA) (100 nM) treatment. Fractionation of the cytosolic extracts from mitogen- or TPA-treated cells on Sephacryl S-300, TSK-400, and DEAE-Sephacel columns gave results suggesting that a single stimulated kinase accounted for the enhanced S6 and RRLSSLRA phosphorylating activities. The mitogen-activated kinase had an apparent Mr of about 85,000 as determined with Sephacryl S-300, but eluted with an apparent Mr of 26,000 from a TSK-400 high pressure liquid chromatography column. The S6 kinase was also stimulated in cytosols from insulin-like growth factor 1- (100 nM), vasopressin- (250 nM), prostaglandin F2 alpha- (250 nM), and 10% fetal calf serum-treated cells but not from quiescent cells exposed to beta-transforming growth factor (2 ng/ml). TPA, vasopressin and prostaglandin F2 alpha appeared to stimulate this kinase via a protein kinase C-dependent mechanism, since the responses to these hormones, but not to platelet-derived growth factor, epidermal growth factor, and insulin, were lost in protein kinase C-depleted cells.
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PMID:Mitogen-activated S6 kinase is stimulated via protein kinase C-dependent and independent pathways in Swiss 3T3 cells. 330 94

Ascitic fluid form ovarian cancer patients (n = 16), but not from patients with other cancers or with benign diseases, contains a growth-promoting activity which induces the proliferation of both fresh ovarian cancer cells (n = 5) and the ovarian cancer cell line HEY. The ascitic fluid growth factor(s) appears to signal cells through binding and activation of specific, saturable, high-affinity cell surface receptors. Incubation of fresh or cultured ovarian cancer cells with a partially purified preparation of ascitic fluid stimulates phosphatidylinositol turnover and increases cytosolic-free calcium. Each of these biochemical events has been implicated in the action of growth factors. Purified preparations of previously identified growth factors including epidermal growth factor, transforming growth factor-beta, tumor necrosis factor, platelet-derived growth factor, thrombin, insulin, interleukin-1, interleukin-2, vasopressin, angiotensin, alpha- and gamma-interferons, and fibroblast growth factor did not increase cytosolic-free calcium in either fresh ovarian cancer cells or HEY cells. Therefore, ascitic fluid appears to contain one or more previously unidentified growth factors which activate ovarian cancer cells through phosphatidylinositol hydrolysis and resultant changes in cytosolic-free calcium.
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PMID:A putative new growth factor in ascitic fluid from ovarian cancer patients: identification, characterization, and mechanism of action. 342 89

Normal cells require growth factors to multiply. One group of growth factors such as platelet-derived growth factor, bombesin and vasopressin in fibroblasts or antigen in lymphocytes uses a specific inositol lipid as part of a transduction mechanism for generating intracellular mitogenic signals. These growth factors stimulate the hydrolysis of phosphatidylinositol 4,5-bisphosphate to give diacylglycerol (DG) and inositol 1,4,5-trisphosphate (Ins1,4,5P3). The DG remains within the plane of the membrane to activate protein kinase C, one function of which is to increase intracellular pH by switching on a Na+/H+ exchanger. The other product, Ins1,4,5P3, functions as a second messenger to mobilize calcium from intracellular stores. These two ionic events, the increase in pH and calcium, contribute to the onset of DNA synthesis. The hydrolysis of an inositol lipid is a key event in this signal pathway which mediates the action of competence factors. A separate signal pathway, perhaps based on tyrosine phosphorylation, carries out the effects of progression growth factors such as epidermal growth factor (EGF) and insulin. It is argued that oncogenes may be arranged into groups associated with specific signal pathways. For example, the sis oncogene encodes platelet-derived growth factor which might use the src gene product as part of its transduction mechanism to generate the second messengers DG, Ins1,4,5P3 and calcium. These last then act to stimulate the transcription of myc and fos. On the other hand, the erbB gene encodes a protein which resembles the receptor for EGF. The function of the ras protein remains a major unsolved problem but there is indirect evidence for proposing that it may mediate the action of progression factors such as EGF or insulin.
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PMID:Growth factors, oncogenes and inositol lipids. 377 62

The results presented here show that disruption of the microtubule network acts synergistically with cAMP-elevating agents to stimulate the entry into DNA synthesis of 3T3 cells. Antimicrotubule agents and increased cAMP levels require an additional growth-promoting factor for inducing initiation of DNA synthesis; such requirement can be furnished by insulin, vasopressin, epidermal growth factor, platelet-derived growth factor, or fibroblast-derived growth factor. The involvement of the microtubules is indicated by the fact that enhancement of the DNA synthetic response was demonstrated with the chemically diverse agents colchicine, nocodazole, vinblastine, or demecolcine, all of which elicited the response in a dose-dependent manner. We verified that colchicine and nocodazole, at the doses used in this study, induced microtubule disassembly in the absence as well as in the presence of cAMP-elevating agents as judged by measurement of [3H]colchicine binding of total and pelletable tubulin. The involvement of cAMP was revealed by increasing its endogenous production by cholera toxin or by treatment with 8BrcAMP. The enhancing effects of antimicrotubule drugs and cAMP-elevating agents could be demonstrated by incorporation of [3H]thymidine into acid-insoluble material, autoradiography of labeled nuclei, or flow cytofluorometric analysis. The addition of antimicrotubule drugs does not increase the intracellular level of cAMP nor does addition of cAMP-elevating agents promote disassembly of microtubules (as judged by measuring [3H]colchicine binding of total and pelletable tubulin) in 3T3 cells. In view of these findings and the striking synergistic effects between these agents in stimulating DNA synthesis in the presence of a peptide growth factor, we conclude that increased cAMP levels and a disrupted microtubule network regulate independent pathways involved in proliferative response.
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PMID:Interplay of cyclic AMP and microtubules in modulating the initiation of DNA synthesis in 3T3 cells. 618 42

Bombesin is shown to be a potent mitogen for Swiss 3T3 cells. At nanomolar concentrations the peptide markedly enhances the ability of fresh serum to stimulate DNA synthesis in confluent and quiescent cultures of these cells. In the presence of a low concentration (3.5%) of serum, bombesin stimulates 3T3 cell proliferation. In serum-free medium, bombesin induces DNA synthesis in the absence of any other added growth factor; half-maximal effect is obtained at 1 nM. The mitogenic effect of bombesin is dependent on dose and time, is mimicked by litorin, and is markedly potentiated by insulin, colchicine, platelet-derived growth factor, and fibroblast-derived growth factor. These mitogens increase the maximal response elicited by bombesin and decrease the bombesin concentration required to produce half-maximal effect (from 1 nM to 0.3 nM). In contrast, vasopressin, phorbol esters, or cAMP increasing agents fail to enhance the maximal level of DNA synthesis induced by bombesin. Bombesin and litorin may provide useful model peptides for studies on the mechanism(s) by which extracellular ligands control cell proliferation.
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PMID:Bombesin stimulation of DNA synthesis and cell division in cultures of Swiss 3T3 cells. 634 74

Addition of the growth-promoting agents phorbol esters, vasopressin, platelet-derived growth factor or fresh serum to quiescent cultures of Swiss 3T3 cells causes a significant increase in the uptake of 5,5-dimethyl oxazolidine-2-4-dione (DMO), a sensitive measure of intracellular pH. The results further indicate that cytoplasmic alkalinization is an early event associated with the action of a variety of mitogenic compounds.
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PMID:Serum, platelet-derived growth factor, vasopressin and phorbol esters increase intracellular pH in Swiss 3T3 cells. 658 Sep 5

Utilizing [3H]phorbol dibutyrate [P(Bu)2], we have developed an assay for high-affinity phorbol ester receptors in intact rat embryo fibroblasts. At 37 degrees C, binding of [3H]P(Bu)2 reached a maximum within 10 min and was rapidly reversible. The tumor promoters 12-O-tetradecanoyl-phorbol 13-acetate, teleocidin B, and mezerein were potent inhibitors of [3H]P(Bu)2 binding. Phorbol and 4-alpha-phorbol didecanoate, which lack tumor-promoting activity, did not inhibit [3H]P(Bu)2 binding. Epidermal growth factor, platelet-derived growth factor, fibroblast growth factor, arginine and lysine vasopressin, luteinizing-hormone releasing hormone, and diazepam did not inhibit [3H]P(Bu)2 binding. A Scatchard analysis was compatible with two classes of binding sites, one with Kd = 8 nM and about 1--2 x 10(5) sites per cell and the other with Kd = 710 nM and about 3 x 10(6) sites per cell. Sera from various species, human amniotic fluid, and certain tissue extracts inhibited specific binding of [3H]P(Bu)2. Fractionation of human serum led to 135-fold purification of an inhibitory factor with a molecular weight in the range 40,000 to 80,000.
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PMID:Identification of receptors for phorbol ester tumor promoters in intact mammalian cells and of an inhibitor of receptor binding in biologic fluids. 694 Dec 90

Addition of Na+ to Na+-depleted Swiss 3T3 cells causes a rapid and dramatic increase in intracellular pH, as monitored by uptake of the weak acid 5,5-dimethyloxazolidine-2,4-dione. The effect of Na+ is concentration dependent (half-maximal effect at 38 mM); this cation can be replaced by Li+ but not by K+ or the choline ion. Amiloride prevents the Na+-induced increase in intracellular pH and also blocks the entry of Na+ into 3T3 cells; the half-maximal concentrations of amiloride for inhibiting the two processes are similar (40 microM). Increase in extracellular pH caused an increase in the initial rate of Na+ influx that was of sufficient magnitude to stimulate the activity of the Na+/K+ pump in quiescent 3T3 cells. Taken together, these findings suggest the presence of a functional Na+/H+ antiport in Swiss 3T3 cells. Addition of the potent mitogenic combination platelet-derived growth factor, vasopressin, and insulin to quiescent Swiss 3T3 cells increased the intracellular pH from 7.21 +/- 0.07 to 7.36 +/- 0.09 in 10 independent experiments (P less than 0.001). This combination of growth factors also stimulated Na+ entry and ouabain-sensitive Rb+ uptake. The data support the hypothesis that early changes in ion fluxes play a role in signaling mitogenesis in 3T3 cells.
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PMID:Na+/H+ antiport in Swiss 3T3 cells: mitogenic stimulation leads to cytoplasmic alkalinization. 696 50

A causal or supportive relationship between 1,2-diacylglycerol (DAG) content and the maintenance of tonic vasoconstriction was sought in canine basilar arteries treated in vitro with various agents reported to increase DAG levels in other tissues (platelet-derived growth factor, vasopressin, angiotensin II, and endothelin-1) and, conversely, with agents known to activate sustained constriction (high K+, phorbol ester, hemolysate, and endothelin-1). Multiple segments from individual isolated arteries were prepared. Some segments were immediately frozen as controls and others incubated in physiological saline solution at 37 degrees C for either 5 minutes or 30 minutes in the presence or absence of different concentrations of the test materials. Segments were then quickly frozen until homogenized for lipid extraction and DAG assay. The DAG content of samples incubated up to 2 hours in physiological saline solution alone did not significantly differ from that of immediately frozen control samples. Resting DAG content expressed relative to total protein measured in each sample averaged 3.82 +/- 0.26 (standard error of the mean) pmol DAG/microgram of protein (74 samples from 37 arteries). Endothelin at 2 x 10(-7) mol/L led to a statistically significant increase in DAG content of approximately 40% of basal content at 5 and 30 minutes. A smaller increase in DAG attributable to hemolysate (approximately 25%) was statistically significant at 30 minutes, whereas vasopressin provoked a notable decrease in DAG content. The other agents had no effect. No differences in these results were noted between normal canine basilar arteries and arteries constricted in vivo by subarachnoid blood clot before isolation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of vasoconstrictor agents on diacylglycerol content of normal and vasospastic canine basilar arteries in vitro. 759 11

We analyzed the effect of growth factors on the localization of the 80-kDa acidic myristoylated alanine-rich C-kinase substrate (80-kDa MARCKS), the major protein kinase C (PKC) substrate, in Swiss 3T3 fibroblasts. Virtually all 80-kDa MARCKS of quiescent cultures of these cells was membrane bound. However, within 40 min after addition of bombesin (10 nM) to these cells, the content of 80-kDa MARCKS in the cytoplasmic fraction increased 25-fold. Phosphorylated 80-kDa MARCKS was detectable in the cytoplasmic fraction as early as 30 s after addition of bombesin and the translocation was sustained for 6 h i.e. until 80-kDa MARCKS became down-regulated. The ability of bombesin to stimulate translocation of 80-kDa MARCKS was dose-dependent (concentration required to produce 50% of the effect was 0.6 nM bombesin) and was abolished by the specific antagonist [Leu14,13 psi 14CH2NH]bombesin. Furthermore, platelet-derived growth factor (PDGF) stimulated a dose-dependent (concentration required to produce 50% of the effect was 3 ng/ml) translocation which was comparable to that induced by bombesin in terms of kinetics and magnitude. Translocation was independent of continuous protein synthesis, but dependent on active PKC. Depletion or inhibition of PKC activity abolished the 80-kDa MARCKS translocation induced by either bombesin or PDGF. Furthermore, the neuropeptides beta-endothelin, bradykinin, and vasopressin, which are known to stimulate PKC activity, also promoted translocation. In contrast, epidermal growth factor, insulin and forskolin, which do not activate PKC, failed to cause such an effect. Translocation of 80-kDa MARCKS was also observed in Rat1 cells treated with phorbol ester, PDGF and beta-endothelin. We conclude that the translocation of 80-kDa MARCKS from the membrane to the cytosol is an early response to a variety of growth-promoting factors that stimulate PKC through different signal-transduction pathways.
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PMID:Bombesin, endothelin and platelet-derived growth factor induce rapid translocation of the myristoylated alanine-rich C-kinase substrate in Swiss 3T3 cells. 795 68


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