Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sites of specific binding of 3H-L-dihydroalprenolol (3H-DHA) were identified on the surface of ascites sarcoma 37 cells, using competitive displacement and binding of the beta-adrenergic antagonists, 3H-DHA and L-propranolol. These binding sites possessed the properties of beta-adrenergic receptors coupled with adenylate cyclase. Analysis of 3H-DHA binding by the Scatchard method revealed the presence of beta-adrenergic receptors of two types, i. e., with a high (Kd = 0.9-1.0 nM) and low (Kd = 15-20 nM) affinity for 3H-DHA. The number of high affinity receptors was (5.0-7.5) X 10(3); that of low affinity receptors was (20-30) X 10(3) on a per cell basis. Sarcolysine at concentrations of 1-10 microM displaced receptor-bound 3H-DHA, competed with the ligand for the common binding sites and caused, similar to isoproterenol, a short-term elevation of the intracellular cAMP content. Sarcolysine within the same concentration range (2.5-25 microM) caused non-competitive inhibition of the cAMP phosphodiesterase (PDE2) activity of plasma membranes isolated from ascites sarcoma 37 cells. The data obtained point to the functional coupling between beta-adrenergic receptors, adenylate cyclase and membraneous PDE2 of tumour cells as well as to its possible role in the antitumour effect of sarcolysine.
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PMID:[Interaction of sarcolysine with beta-adrenoreceptors in tumor cells]. 299 89

The plasminogen activator (PA) in clonal osteogenic sarcoma cells of rat origin (UMR 106-01 and UMR 106-06) and in osteoblast-rich rat calvarial cells has been characterized using specific antibodies to be tissue-type PA (tPA). An Mr value of 75,000 by SDS-polyacrylamide gel electrophoresis and fibrin autoradiography supports this characterization. There was also evidence for an Mr 105,000 component, which could be due to a proteinase-inhibitor complex. The mechanism of regulation of this tPA activity has been studied in the clonal osteogenic sarcoma cells. Parathyroid hormone (PTH) and prostaglandin E2, which increase cyclic AMP production in the sarcoma cells, also increased tPA activity. The sensitivity and magnitude of the tPA response to PTH and prostaglandin E2 were increased by simultaneous treatment with isobutylmethylxanthine (IBMX) at drug concentrations which had little effect themselves on tPA activity. In UMR 106-06 cells, which unlike UMR 106-01 cells show a cyclic AMP response to calcitonin, tPA activity was also increased in response to calcitonin, and the effect was enhanced by IBMX. 1,25-Dihydroxyvitamin D-3 also increased tPA activity in the cells, but this response was not modified by IBMX. Synthetic peptide antagonists of PTH-responsive adenylate cyclase, [34Tyr]-hPTH (3-34) amide and [34Tyr]-hPTH (5-34) amide, inhibited the PTH-induced increase in tPA activity over the same concentration range at which they inhibited cyclic AMP production, but the antagonist peptides had no effect on the tPA responses to prostaglandin E2, calcitonin or 1,25-dihydroxyvitamin D-3. These data indicate that cyclic AMP mediates the actions of PTH, prostaglandin E2 and calcitonin in increasing tPA activity in the clonal osteogenic sarcoma cells. 1,25-Dihydroxyvitamin D-3, on the other hand, increases tPA activity through a mechanism independent of cyclic AMP.
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PMID:Cyclic AMP-dependent and -independent effects on tissue-type plasminogen activator activity in osteogenic sarcoma cells; evidence from phosphodiesterase inhibition and parathyroid hormone antagonists. 301 47

The activity of the adenylate cyclase catalytic subunit is higher in Harvey and Kirsten Murine Sarcoma Viruses-infected thyroid epithelial cells than in uninfected control cells either in the presence of Mg2+ alone or following stimulation by Mn2+ or forskolin. The higher activity is associated with an increased cAMP cellular content. The Gpp(NH)p and F- anion are more effective positive modulators in the control than in the virus infected cells: these results exclude therefore that the ras p21 proteins can act as the G-protein alpha-subunit and suggest that they negatively interfere with the G-protein modulation of the adenylate cyclase system.
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PMID:Increased adenylate cyclase activity in rat thyroid epithelial cells expressing viral ras genes. 302 15

Rat kidney (NRK) cells infected with a temperature-sensitive mutant of the Kirsten sarcoma virus were arrested in the G0/G1 phase of their cell cycle by incubation in serum-deficient medium at a p21-inactivating temperature of 41 degrees C. These quiescent ts K-NRK cells were then stimulated to transit G1 and initiate DNA replication by lowering the temperature to 36 degrees C, which rapidly reactivated p21. Reactivating the viral Ki-RAS protein by temperature shift led to an increase in adenylate cyclase activity in early G1 phase. The Ki-RAS protein increased the sensitivity of adenylate cyclase to guanyl nucleotides by a mechanism that seemed to involve inactivation of the enzyme's inhibitory G1 regulatory protein.
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PMID:Viral p21 Ki-RAS protein: a potent intracellular mitogen that stimulates adenylate cyclase activity in early G1 phase of cultured rat cells. 355 14

tsK-NRK rat cells infected with a temperature-sensitive mutant of the Kirsten murine sarcoma virus were arrested in the G0/G1 phase of their cell cycle by incubation in serum-deficient medium at a temperature (41 degrees C) which inactivates the virus' abnormally thermolabile mitogenic/oncogenic 21 kDa (p 21) RAS protein product. Reactivating the viral RAS protein by lowering the temperature to a permissive 36 degrees C rapidly (within 1 hour) stimulated adenylate cyclase, sensitized the enzyme to stimulation by GTP and forskolin and caused the tsK-NRK cells to transit G1 and start replicating their DNA about 10 hours later. The 41 degrees C----36 degrees C shift did not affect adenylate cyclase or stimulate G1 transit in uninfected NRK cells. Thus, an oncogenic viral RAS protein was able to stimulate adenylate cyclase and G1 transit in a mammalian cell just as other RAS proteins appear to do in yeast cells.
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PMID:The mitogenic/oncogenic p21 Ki-RAS protein stimulates adenylate cyclase activity early in the G1 phase of NRK rat kidney cells. 390 56

Harvey (Ha-MSV) and Kirsten (Ki-MSV) murine sarcoma viruses induce tumours in animals and transform various cells in culture because of the expression of the ras oncogene product, p21 (ref. 1). Proto-oncogenes homologous with these genes are highly conserved evolutionarily and activated ras oncogenes have been detected in many human cancers. Whether c-ras oncogenes are directly responsible for human carcinogenesis is uncertain; however, it is clear that p21 mediates virus-induced transformation, although by an unknown mechanism. Epithelial and fibroblast cell lines transformed with Ha-MSV and Ki-MSV express p21 (ref. 8) and exhibit reduced adenylate cyclase activity. Like the guanine nucleotide regulatory proteins, Ns and Ni, which mediate stimulation and inhibition, respectively, of adenylate cyclase, p21 is a membrane-associated GTP binding protein, which exhibits GTPase activity. These similarities suggest that p21 and the adenylate cyclase regulatory proteins are related in cellular function, and that p21 depresses adenylate cyclase by inhibiting the activity of Ns or acting as Ni. We have therefore now examined the structural and functional similarities between p21 and Ns and Ni and find no evidence that p21 regulates adenylate cyclase activity by acting as one of these regulatory proteins.
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PMID:The ras oncogene product p21 is not a regulatory component of adenylate cyclase. 392 44

The binding of [3H]prostaglandin E1 to membranes of clones of normal rat kidney fibroblasts (NRK cells) has been measured. Cell lines that responded to prostaglandin E1, such as NRK and NRK transformed with Schmitt-Ruppin strain of Rous sarcoma virus (SR-NRK cells), have a high affinity prostaglandin E1 binding site. Murine-sarcoma-virus-transformed lines of NRK cells are unresponsive to prostaglandin E1 and have reduced prostaglandin E1 binding Exposure of cells to prostaglandin E1 results both in decreased prostaglandin E1 responsiveness and reduced prostaglandin E1 binding. Activation of adenylate cyclase is correlated to binding of prostaglandin E1 to receptors in both NRK and SR-NRK cell membranes. Mathematical models suggest that GTP decreases the affinity of hormone for its receptor while increasing the catalytic efficiency of adenylate cyclase, and that aggregates of occupied receptors may play an important role in the activation of adenylate cyclase.
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PMID:Prostaglandin E1 binding and adenylate cyclase activation in normal and transformed fibroblasts. 624 20

A doubly transformed rat glioma cell line, designated C6V-1, was obtained from rat glioma C6 cells by infection with a rat-adapted variant of Moloney sarcoma virus (MSV-M-os). The C6V-1 cells show karyotypic changes in chromosome number (43) and structure, while C6 cells possess a normal male karyotype. C6V-1 and C6 cells were employed for characterization of a receptor-adenylate cyclase system of the surface membrane. C6V-1 cells showed lower adenylate cyclase activity than that of C6 cells, though the apparent Km for ATP in both types of cells was the same. The maximal stimulation of adenylate cyclase by isoproterenol was significantly reduced, and Kact for isoproterenol was approximately 18-fold lower in C6V-1 cells. When the concentration of beta-adrenergic receptors was measured by various concentrations of [3H] dihydroalprenolol (DHA), the maximal binding sites of C6 and C6V-1 cells were 760 and 230 fmol/mg protein, respectively, without any changes in the association constant for DHA. The concentration of isoproterenol required for 50% displacement of the [3H] DHA binding (Kd) was the same (around 1.5 X 10(-6)M) in both cells, measured in the presence of GTP. Thus the 19-fold drop in the Kd/Kact ratio in C6V-1 cells suggests an incomplete coupling of beta-receptors to adenylate cyclase. Cyclic AMP phosphodiesterase activity and cAMP content in C6V-1 were lower than in C6 cells. Mitochondrial monoamine oxidase and cytosomal enolase activities, however, were somewhat higher in C6V-1 cells. The results indicate that a set of changes in the receptors and in the cyclic AMP system of C6V-1 is one of the specific alterations by transformation, even though those may not be the cause of cell transformation.
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PMID:Receptor-associated changes of the catecholamine-sensitive adenylate cyclase in glioma cells doubly transformed with Moloney sarcoma virus. 627 81

A kidney cell line (MDCK) retains an adenylate cyclase system sensitive to glucagon, vasopressin, isoproterenol and prostaglandin E1. The stimulatory effect of glucagon on cAMP production was selectively lost in a cloned line derived from MDCK cells transformed by Harvey murine sarcoma virus. Sensitivity to glucagon was largely restored by treatment of the transformed cells with prostaglandin E1 or butyrate. Loss and reappearance of glucagon receptors seemed to be responsible for the observation. The parental MDCK line produced prostaglandins and in the transformed line, this function was abolished. These observations suggest that synthesis of glucagon receptors is controlled by endogenously produced prostaglandin in MDCK cells and that loss of glucagon receptors and their responsiveness in the transformed cells occurs as a consequence of the inability of these cells to synthesize this prostaglandin.
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PMID:Loss and restoration of glucagon receptors and responsiveness in a transformed kidney cell line. 629 63

Certain metabolic properties of hormonally responsive osteogenic sarcoma cells derived from a transplantable rat tumor have been compared with those of related normal rat bone cells. All studies were carried out on cells grown in monolayer culture. Normal rat bone cells derived by repeated collagenase/trypsin digestion of newborn rat calvaria. Bone cells selected for comparison were thought to be osteoblast-like, as judged by enrichment of alkaline phosphatase and adenylate cyclase responsiveness to parathyroid hormone and prostaglandin E2. The adenylate cyclases of the two cell strains were similarly stimulated by a range of prostanoids and their metabolites and analogs. Morphology showed the two cell strains to be similar; the only obvious difference was a multilayering of cells in the sarcoma cultures, while the normal cultures showed abundant extracellular fibril formation which was not seen in the tumor cells. Investigation of the cAMP-dependent protein kinase isoenzymes showed the presence of two forms in both cell types, one eluting at a low salt concentration and the other at a high salt concentration. There was approximately twice the amount of the first isoenzyme compared to the second isoenzyme. The results indicate the usefulness of the two cell strains to elucidate further the molecular mechanisms of action of parathyroid hormone and prostaglandins.
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PMID:Functional properties of hormonally responsive cultured normal and malignant rat osteoblastic cells. 693 60


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