Cyclic 3′,5′-Adenosine Monophosphate Phosphodiesterase Produced by the Slime Mold
            <i>Dictyostelium discoideum</i>

Chang, Ya-Hui

doi:10.1126/science.161.3836.57

Cited by 183 publications

(53 citation statements)

References 20 publications

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“…The hydrolysis of cGMP to 5'-GMP is performed by two cyclic nucleotide phosphodiesterase activities: a small phosphodiesterase activity hydrolyzing cAMP and cGMP at approximately the same rate and a large activity specific for cGMP (Chang, 1968;. cGMP stimulates the latter enzyme about threefold by decreasing the Km of the enzyme at an unaltered Vmax (Bulgakow and Van Haastert, 1983 where a and ,B are the basal and receptor-stimulated activity of phospholipase C, respectively (Bominaar et al, 1994), and y is the first order rate constant of IP3 degradation (Van Lookeren Campagne et al., 1988).…”

Section: Methodsmentioning

confidence: 99%

“…Although the peak values of the cGMP response depend on the stimulus concentration, the kinetics of the response is essentially independent with respect to the cAMP concentration. Extracellular cAMP is degraded by phosphodiesterase activity in the medium (Chang, 1968;Malchow et al, 1972;Panbacker and Bravard, 1972). The magnitude and kinetics of the cGMP response remain the same whether the cAMP stimulus is present for only 3 s or is not degraded at all (Van Haastert and Van der Heyden, 1983).…”

Section: Introductionmentioning

confidence: 99%

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A model for cAMP-mediated cGMP response in Dictyostelium discoideum.

Valkema

Haastert

1994

MBoC

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In Dictyostelium discoideum extracellular cyclic AMP (cAMP), as shown by previous studies, induces a transient accumulation of intracellular cyclic guanosine-5'-monophosphate (cGMP), which peaks at 10 s and recovers basal levels at 30 s after stimulation, even with persistent cAMP stimulation. Additional investigations have shown that the cAMP-mediated cGMP response is built up from surface cAMP receptor-mediated activation of guanylyl cyclase and hydrolysis of cGMP by phosphodiesterase. The regulation of these activities was measured in detail on a seconds time-scale, demonstrating complex adaptation of the receptor, allosteric activation of cGMP-phosphodiesterase by cGMP, and potent inhibition of guanylyl cyclase by Ca2 . In this paper we present a computer model that combines all experimental data on the cGMP response. The model is used to investigate the contribution of each structural and regulatory component in the final cGMP response. Four models for the activation and adaptation of the receptor are compared with experimental observations. Only one model describes the magnitude and kinetics of the response accurately. The effect of Ca21 on the cGMP response is simulated by changing the Ca21 concentrations outside the cell (Ca2+ influx) and in stores (IP3-mediated release) and changing phospholipase C activity. The simulations show that Ca21 mainly determines the magnitude of the cGMP accumulation; simulations are in good agreement with experiments on the effect of Ca2+ in electropermeabilized cells. Finally, when cGMP-phosphodiesterase activity is deleted from the model, the simulated cGMP response is elevated and prolonged, which is in close agreement with the experimental observations in mutant stmF that lacks this enzyme activity. We conclude that the computer model provides a good description of the observed response, suggesting that the main structural and regulatory components have been identified.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A model for cAMP-mediated cGMP response in Dictyostelium discoideum.

Valkema

Haastert

1994

MBoC

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“…This last observation might explain why all the classical phosphodiesterase inhibitors (caffeine, theophylline) fail to inhibit the slime mold phosphodiesterase [40].…”

Section: Specijicity Of the Beef Heart Phosphodiesterasementioning

confidence: 99%

Substrate Specificity of Cyclic Nucleotide Phosphodiesterase from Beef Heart and from Dictyostelium discoideum

et al. 1983

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The substrate specificity of beef heart phosphodiesterase activity and of the phosphodiesterase activity at the cell surface of the cellular slime mold Dicfyostelium discoideum has been investigated by measuring the apparent K, and maximal velocity (V) of 24 derivatives of adenosine 3',5'-nionophosphate (CAMP). Several analogs have increased K,,, values, but unaltered V values if compared to CAMP; also the contrary (unaltered X, and reduced V) has been observed, indicating that binding of the substrate to the enzyme and ring opening are two separate steps in the hydrolysis of CAMP.cAMP is bound to the beef heart phosphodiesterase by dipole-induced dipole interactions between the adenine moiety and an aromatic amino acid, and possibly by a hydrogen bond between the enzyme and one of the exocyclic oxygen atoms; a cyclic phosphate ring is not required to obtain binding. cAMP is bound to the slime mold enzyme via a hydrogen bond at the 3'-oxygen atom, and probably via a hydrogen bond with one of the exocyclic oxygen atoms. A cyclic phosphate ring is necessary to obtain binding to the enzyme. A specific interaction (polar or hydrophobic) between the base moiety and the enzyme has not been demonstrated. A negative charge on the phosphate moiety is not required for binding of cAMP to either enzyme.The catalytic reaction in both enzymes is restricted to the phosphorus atom and to the exocyclic oxygen atoms. Substitution of the negatively charged oxygen atom by an uncharged dimethylamino group in axial or equatorial position renders the compound non-hydrolyzable. Substitution of an exocyclic oxygen by a sulphur atom reduces the rate of the catalytic reaction about 100-fold if sulphur is placed in axial position and more than 10000-fold if sulphur is placed in equatorial position. A reaction mechanism for the enzymatic hydrolysis of cAMP is proposed.cAMP is a key regulator of metabolism, function and growth of many cell types [l]. In mammalian cells CAMP is the second messenger of many hormones; it achieves its function via binding to an intracellular receptor, which is a protein kinase. In the cellular slime mold Dicfyostelium discoideum cAMP acts as the first messenger [2]; it is excreted by the cells and achieves its function via binding to a cell surface receptor. In D. discoideum cAMP induces chemotaxis and cell aggregation (for reviews see [3,4]).The level of cAMP is controlled by the rate of synthesis catalyzed by adenylate cyclase, the rate of excretion, and the rate of degradation by cyclic nucleotide phosphodiesterase.In mammalian tissue at least three types of phosphodiesterase have been demonstrated : a calmodulin-dependent enzyme, a CAMP-specific enzyme, and a third form characterized by cGMP activation (for reviews see [5,6]). In the cellular slime molds at least two enzymes have been demonstrated: one enzyme is localized on the cell surface and in the extracellular medium [7,8] and hydrolyzes cAMP and cGMP with about equal rates, and one cGMP-specific enzyme is localized intracellularly [9-111. cAMP and c...

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“…In relaying a cAMP wave, precocious cells in a starved population release pulses of the chemoattractant cAMP that stimulate adjacent cells to release, in turn, a pulse of cAMP (Gerisch et al, 1975;Devreotes and Steck, 1979). Through the activity of extracellular phosphodiesterase, cAMP is then degraded (Chang, 1968;Riedel and Gerisch, 1971;Dinauer et al, 1980), which results in a cAMP signal that is relayed outwardly through the cell population as a non-dissipating, symmetrical wave (Tomchik and Devreotes, 1981;Soll et al, 2002). The spatial and temporal gradients of cAMP in the front and back of each relayed wave, which pass across cells on average every 7 minutes, are then assessed by each cell in the aggregating population, resulting in directed movement towards the aggregation center in the front of each wave of cAMP (Soll et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Ca2+ chemotaxis inDictyostelium discoideum

Scherer

Kuhl

Wessels

et al. 2010

Journal of Cell Science

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SummaryUsing a newly developed microfluidic chamber, we have demonstrated in vitro that Ca 2+ functions as a chemoattractant of aggregationcompetent Dictyostelium discoideum amoebae, that parallel spatial gradients of cAMP and Ca 2+ are more effective than either alone, and that cAMP functions as a stronger chemoattractant than Ca 2+ . Effective Ca 2+ gradients are extremely steep compared with effective cAMP gradients. This presents a paradox because there is no indication to date that steep Ca 2+ gradients are generated in aggregation territories. However, given that Ca 2+ chemotaxis is co-acquired with cAMP chemotaxis during development, we speculate on the role that Ca 2+ chemotaxis might have and the possibility that steep, transient Ca 2+ gradients are generated during natural aggregation in the interstitial regions between cells.

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Cyclic 3′,5′-Adenosine Monophosphate Phosphodiesterase Produced by the Slime Mold Dictyostelium discoideum

Cited by 183 publications

References 20 publications

A model for cAMP-mediated cGMP response in Dictyostelium discoideum.

A model for cAMP-mediated cGMP response in Dictyostelium discoideum.

Substrate Specificity of Cyclic Nucleotide Phosphodiesterase from Beef Heart and from Dictyostelium discoideum

Ca2+ chemotaxis inDictyostelium discoideum

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