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Target Concepts:
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Query: EC:4.6.1.1 (
adenylate cyclase
)
19,190
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Binding of an intrinsic agonist (cAMP) to specific receptors on the cell surface induces transmembrane signals for activation and desensitization (adaptation and down regulation) of
adenylate cyclase
in the cellular slime mold, Dictyostelium discoideum. It is generally believed that dithiothreitol (DTT) induces the activation through interaction between the receptor and gradually accumulated cAMP, since DTT is known to inhibit cAMP-phosphodiesterase which degrades cAMP. In the present paper, we investigated the mechanism of activation of
adenylate cyclase
by the thiol-reducing agents, DTT and
2,3-dimercapto-1-propanol
(BAL). We found that BAL activated
adenylate cyclase
transiently even under conditions where the intrinsic agonist supersaturated the cAMP-receptors and competitively inhibited phosphodiesterase. This result is inconsistent with the generally accepted notion. We conclude that BAL has an independent effect from those of the intrinsic agonist (cAMP) and phosphodiesterase in activation of
adenylate cyclase
. Since BAL could induce activation just after the activation induced by a supersaturating concentration of the intrinsic agonist had ceased, the independent effect of BAL is not a simple enhancement of the cAMP-induced activation. Our result also suggests that the cAMP-induced adaptation (but not down regulation) suppresses the BAL-induced activation while BAL itself does not induce adaptation to cAMP or BAL. We propose that the thiol-reducing reagent induces or modifies the transmembrane activation signal for
adenylate cyclase
.
...
PMID:Reducing reagent-induced activation of adenylate cyclase in the cellular slime mold, Dictyostelium discoideum. 166 89
Two substances, cAMP and
2,3-dimercapto-1-propanol
(BAL) are known to induce transient activation of
adenylate cyclase
in Dictyostelium discoideum. A frigid mutant (HC85) has a deletion in a gene for G alpha 2, a guanine nucleotide binding protein and cannot activate the cyclase in response to cAMP. We found that BAL induced activation in the frigid mutant. This result suggests that the BAL-induced activation is independent of G alpha 2 and that BAL mimics a role of activated G alpha 2. We also found that cAMP promoted the BAL-induced activation. This result suggests that cAMP plays a role in activation through a mechanism in which G alpha 2 is not involved. We lastly showed that continuous cAMP stimulation could not inhibit the BAL-induced activation in the frigid mutant. Since the cAMP-induced inhibition observed in the wild type strain (NC4) proceeds with the time course identical to the cAMP-induced adaptation (Oyama, submitted), this result suggests that G alpha 2 is involved in adaptation of
adenylate cyclase
.
...
PMID:Role of a guanine nucleotide binding protein, G alpha 2, in regulation of adenylate cyclase in Dictyostelium discoideum. 190 Jan 54
Binding of cyclic AMP (cAMP) to cell surface receptors induces activation and adaptation of
adenylate cyclase
while
2,3-dimercapto-1-propanol
(BAL) acts only on the activation pathway. Here we show that an inhibitor of protein kinase (K252a) inhibits the cAMP-induced activation of the cyclase but not (rather enhances) the BAL-induced activation. These results suggest that protein kinase is involved in transduction of the activation signal and that phosphorylation might take place between the receptor and the action site of BAL. Since adaptation causes cessation of the activation, the enhancement of the BAL-induced cAMP accumulation by K252a might imply that K252a also blocks transduction of the adaptation signal.
...
PMID:Involvement of protein kinase(s) in the intracellular signal transduction pathways for activation and adaptation of adenylate cyclase in Dictyostelium discoideum. 215 15
