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

---

Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The B subunit of cholera toxin, a protein which binds specifically to ganglioside GM1 on the cell surface, stimulates DNA synthesis in quiescent Swiss 3T3 fibroblasts as measured by an increase in [3H]thymidine incorporation. Pertussis toxin pretreatment markedly inhibits B subunit-induced DNA synthesis. The inhibitory effects of pertussis toxin were observed even in the presence of insulin which greatly potentiates the mitogenic response to the B subunit. Treatment with either pertussis toxin or insulin did not alter the binding of the B subunit to the cells. The dose-response for pertussis toxin-induced inhibition of DNA synthesis correlated closely with the dose-response for ADP-ribosylation of a 41-kDa membrane protein, suggesting the involvement of a GTP-binding protein that is a substrate for pertussis toxin (Gi) in mitogenesis induced via cross-linking of endogenous gangliosides. Pertussis toxin, in a similar concentration-dependent manner, also inhibited the mitogenic response to unfractionated fetal calf serum and to bombesin in the absence or presence of insulin. The inhibitory effect of pertussis toxin was clearly unrelated to any effects on known G proteins coupled to adenylate cyclase or phospholipase C. In addition, pertussis toxin did not impair the early increase in cytosolic free Ca2+ induced by the B subunit or bombesin. Pertussis toxin-induced inhibition of DNA synthesis could still be observed even when the toxin was added as late as 6 h after addition of the growth-promoting agents. This suggests the involvement of a GTP-binding protein in a late step of the B subunit- and bombesin-mediated pathways of mitogenesis. The possibility that other growth factors bypass this pathway is shown by their lack of sensitivity to pertussis toxin.
...
PMID:Possible involvement of a GTP-binding protein in a late event during endogenous ganglioside-modulated cellular proliferation. 249 20

We have previously reported that anti-fucosyl GM1 ganglioside antibody partially suppresses cAMP production in FRTL-5 rat thyroid cells not via the TSH receptor but via guanine nucleotide-binding protein indirectly. In order to clarify further the mechanism of the antibody action, we studied the relationship with alpha 2- and beta-adrenergic and adenosine A1 receptors. FRTL-5 cells did not bind [3H]clonidine, suggesting the lack of alpha 2-adrenergic receptor or at least abnormality of its binding domain. On the other hand, the cells specifically bound [125I]iodocyanopindolol, but isoproterenol failed to affect the basal and TSH-stimulated cAMP production indicating the lack of coupling with adenylate cyclase. The inhibition of cAMP production induced by anti-fucosyl GM1 antibody was not altered by adrenergic agents. [125I]hydroxyphenylisopropyl adenosine binding was observed in FRTL-5 cells but was not displaced by the antibody. These results lead to conclusions that FRTL-5 cells lack alpha 2-adrenergic receptor but have beta-adrenergic receptor which lacks coupling with adenylate cyclase and have adenosine A1 receptor, and that the adrenergic receptors and adenosine A1 receptor are not the site of action of anti-fucosyl GM1 antibody.
...
PMID:Alpha 2- and beta-adrenergic receptors and adenosine A1 receptor of FRTL-5 rat thyroid cells in relation to fucosyl GM1 ganglioside. 254 96

The responsiveness of enterocytes to Escherichia coli heat-labile enterotoxin (LT) was studied in the small intestine of 6- to 7-week-old rats. Dose-effect analysis showed the dose required for a 50% maximal LT-induced secretory response to be at 8 nM. After the well-documented glycolipid GM1 receptor was blocked with the cholera toxin B subunit, LT still activated the second messenger cascade, measured in terms of heightened cellular adenylate cyclase activity, and caused fluid to be secreted into ligated intestinal loops. Furthermore, Scatchard analysis of binding kinetics suggested that LT bound to two receptor sites on the intestinal microvillus membrane. The toxin also bound to delipidated membrane but was competitively inhibited by a galactose-specific lectin, RCA60, suggesting that the additional receptor is a galactoglycoprotein. Western blot analysis of toxin binding to membrane proteins revealed a group of binding components around 85 to 150 kilodaltons. When measured at 2.2 nM LT, approximately 70% of LT-binding activity took place through a high-affinity (Kd1, 0.38 nM) GM1 receptor and 30% of LT-binding activity took place through a low-affinity (Kd2, 3.3 nM) glycoprotein receptor. These results suggest that LT functions through two microvillus membrane receptors in the mature rat small intestine.
...
PMID:Host response to Escherichia coli heat-labile enterotoxin via two microvillus membrane receptors in the rat intestine. 267 13

Cholera holotoxin produces both stimulation and inhibition of the growth of different cell populations. These opposite effects were both attributed to the enzymatic activity of the subunit A that activates adenylate cyclase, increasing the intracellular level of cAMP. We observed that the B subunit of cholera toxin produced by itself an inhibition of the 'in vitro' growth of two murine leukemia cell lines (L1210 limphoid leukemia and WEHI-3B myelomonocytic leukemia). The sensitivity of WEHI-3B cells towards cholera toxin was about 5000-times higher than that of the L1210 cells, whereas the two leukemias showed an identical sensitivity to the B subunit (IC50 = 5.10(-10) M for L1210 and 10(-10) M for WEHI-3B). The inhibition produced by the B subunit was neutralized by GM1 and in a minor degree by type II gangliosides. The two leukemias showed a remarkable difference in their gangliosides contents (L1210 cells contained GM1 (80.6%) and GM2 (19.4%), while WEHI-3B cells contained GM1 (28.2%), Fuc-GM1 (44.9%) and a band (26.9%) with a chromatographic mobility between GD1a and GD1b). The inhibition could be explained by a competitive mechanism between the B subunit and some autocrine factor binding GM1-containing receptors. Our data strengthen the suggestion to consider gangliosides as very important pleiotropic biomodulators.
...
PMID:Inhibition of murine leukemia (WEHI-3B and L1210) proliferation by cholera toxin B subunit. 280 81

The B subunit of cholera toxin does not affect the growth of rat glioma C6 cells which are deficient of its receptor, ganglioside GM1. Insertion of ganglioside GM1 into the plasma membrane of C6 cells renders them susceptible to inhibition of DNA synthesis by the B subunit. Exposure of C6 cells to butyrate induces an elevation of ganglioside GM1 as measured by an increase in binding of iodinated cholera toxin and also results in an inhibition of DNA synthesis by the B subunit. The extent of inhibition of DNA synthesis correlated with the binding of B subunit and was independent of adenylate cyclase activation or increases in intracellular cAMP levels.
...
PMID:Insertion of ganglioside GM1 into rat glioma C6 cells renders them susceptible to growth inhibition by the B subunit of cholera toxin. 283 87

The B subunit of cholera toxin, which binds specifically to ganglioside GM1, stimulates DNA synthesis in quiescent Swiss 3T3 fibroblasts grown in chemically defined medium. The mitogenic response to the B subunit was potentiated by insulin and other growth factors. To elucidate the mechanism by which the B subunit stimulates cell growth , its effects on several transmembrane signaling systems which have been suggested to play a vital role in cell growth regulation were examined. The B subunit did not increase cAMP levels nor activate adenylate cyclase. The B subunit induced a rapid and profound increase in intracellular free Ca2+ as measured with the fluorescent Ca2+-sensitive dye quin 2/AM. Removal of external Ca2+ completely inhibited the signal, thus suggesting that the B subunit elevates intracellular Ca2+ through a net influx of extracellular Ca2+ rather than by causing the release of Ca2+ from intracellular stores. These findings are consistent with the observations that the B subunit induced reinitiation of DNA synthesis without activation of phospholipase C. There was no increase in the formation of inositol trisphosphate, the second messenger that mediates release of Ca2+ from intracellular stores. In addition, the B subunit still stimulated DNA synthesis in Swiss 3T3 cells pretreated with phorbol ester to down-regulate protein kinase C. These results suggest that the mitogenic effects of the B subunit are mediated mainly by facilitation of Ca2+ influx and that activations of adenylate cyclase, phospholipase C, or protein kinase C are not obligatory steps in the initiation of cell growth by the B subunit. Furthermore, the observation that Ca2+ ionophores, such as ionomycin and A23187, are not mitogenic implies that additional undefined growth signaling pathways may exist in this system.
...
PMID:Mitogenesis of 3T3 fibroblasts induced by endogenous ganglioside is not mediated by cAMP, protein kinase C, or phosphoinositides turnover. 283 53

In quiescent rat thyroid (FRTL-5) cells, the B subunit of cholera toxin, which binds to cell surface ganglioside GM1 specifically, alone induced DNA synthesis and markedly enhanced that induced by insulin in serum-free medium. On the other hand, the B subunit inhibited DNA synthesis induced by thyrotropin (TSH). The B subunit did not activate adenylate cyclase and had no effect on the TSH-induced cyclic adenosine 3',5'-monophosphate (cAMP) production. Moreover, the B subunit inhibited DNA synthesis induced by dibutyryl cAMP (Bt2cAMP) or phorbol-12-myristate-13-acetate (PMA). These data demonstrate that the B subunit has both stimulatory and inhibitory effects on DNA synthesis in FRTL-5 cells depending on the presence of other growth factors and that these effects on cell proliferation by the interaction of the B subunit, possibly with cell surface ganglioside GM1, may involve a mechanism independent from the modulation of membrane receptor function through interaction with growth factor receptor.
...
PMID:Regulation of proliferation by the cholera toxin B subunit in FRTL-5 cells may involve a mechanism independent from the modulation of membrane receptor function. 284 33

Addition of specific anti-fucosyl GM1 antibody raised in a rabbit caused dose-dependent inhibition of endogenous and thyrotropin (TSH)- or thyroid stimulating antibody-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production in cultured FRTL5 rat thyroid cells. Further, the antibody inhibited the cAMP increase induced by prostaglandin E1 and forskolin. However, anti-fucosyl GM1 antibody did not affect the binding of [125I]bovine TSH to solubilized porcine thyroid TSH receptor or to FRTL5 cells. In conclusion, fucosyl GM1 is one of the specific membrane components of thyrocytes and appears to be involved in adenylate cyclase stimulation or cAMP generation. Further, the biological effects of the ganglioside do not seem to be mediated by the TSH receptor, suggesting a post receptor mechanism.
...
PMID:Biological effect of anti-fucosyl GM1 ganglioside antibody on cyclic adenosine 3',5'-monophosphate production in FRTL5 rat thyroid cells. 288 53

Acute neonatal malnutrition alters lumenal glycoproteins as demonstrated by altered lectin binding. To determine the effect of a 72-h fast on lumenal glycolipids, specifically the monosialoganglioside GM1, we quantitated cholera toxin (CT) binding and adenylate cyclase activity. The calculated number of specific sites for CT binding to microvillus membrane (MVM) from newborn rabbits fasted for 72 h was decreased in MVM from proximal small bowel (7 +/- 0.8 x 10(8)/micrograms protein) compared to 72-h control neonatal rabbits (18 +/- 3.3 x 10(8) micrograms protein). In distal small bowel there was no difference in the calculated receptor sites/micrograms MVM protein between fasted (8 +/- 1.7 x 10(8)) and fed (11 +/- 4 x 10(8)) groups. MVM prepared from proximal small bowel of fed animals bound significantly more CT than MVM prepared from distal small bowel of fed animals. The affinity for CT was the same in all MVM preparations. Neuraminidase treatment of MVM resulted in increased CT binding in fed and fasted rabbit proximal and distal MVM preparations, but the greatest increase occurred in MVM prepared from proximal small bowel from fasted animals. There was no difference in adenylate cyclase activity in fed, fasted, and proximal or distal small bowel crude membrane preparations. Refeeding (120 h) resulted in normalization of CT binding in MVM from proximal small bowel of fasted animals. We conclude a 72-h fast in neonatal rabbits resulted in decreased regional CT binding in MVM prepared from proximal small bowel of fasted animals, but no change in adenylate cyclase activity. Refeeding reverses CT binding abnormalities.
...
PMID:Short term neonatal starvation altered cholera toxin binding in rabbits. 291 2

Cultured NCB-20 hybrid cells express adenylate cyclase-coupled receptors for 5-hydroxytryptamine (5-HT) that correspond biochemically and pharmacologically to 5-HT1 receptors in rodent brain membrane preparations, apart from a much-reduced affinity for 5-HT (160 nM compared to less than 5 nM in brain). Since NCB-20 cells also differ from rodent brain both qualitatively and quantitatively in their ganglioside composition, the effects of exogenously added gangliosides on the affinity of the 5-HT1 receptor for 5-HT were tested. Both GM1 ganglioside (the cholera toxin receptor) and tetrasialoganglioside GQ1b produced a 10-fold increase in receptor affinity for [3H]5-HT, measured by binding studies. All gangliosides, at submicromolar concentrations, resulted in significantly reduced EC50 values for 5-HT-mediated elevation of intracellular cyclic AMP levels. GQ1b had the capacity to most dramatically enhance the potency of 5-HT in mediating increases in cyclic AMP levels. Gangliosides had no effect on the potency of DADLE or 3,4-dihydroxyphenylethylamine (dopamine)-mediated depression of cyclic AMP levels, suggesting some specificity for 5-HT. Our data are interpreted as implying a specific role for polysialogangliosides in modulating the affinity of the 5-HT1 receptor and the coupling of the 5-HT1 receptor-guanine nucleotide binding protein adenylate cyclase complex.
...
PMID:Possible role of gangliosides in regulating an adenylate cyclase-linked 5-hydroxytryptamine (5-HT1) receptor. 299 94


<< Previous 1 2 3 4 5 6 7 8 Next >>

---