scholarly journals Cyclic 3',5'-AMP relay in Dictyostelium discoideum III. The relationship of cAMP synthesis and secretion during the cAMP signaling response.

1980 ◽  
Vol 86 (2) ◽  
pp. 537-544 ◽  
Author(s):  
M C Dinauer ◽  
S A MacKay ◽  
P N Devreotes
Keyword(s):  
Adenylate Cyclase ◽  
Time Course ◽  
Camp Signaling ◽  
Intracellular Camp ◽  
Intact Cells ◽  
Camp Synthesis ◽  
Transient Activation ◽  
Direct Measurements ◽  
Precipitous Decline ◽  
Relationship Of

Refinement of a perfusion technique permitted the simultaneous measurement of cAMP-elicited [3H]cAMP secretion and intracellular [3H]cAMP levels in sensitive D. discoideum amoebae. These data were compared with measurements of the rate of [32P]cAMP synthesis by extracts of amoebae sonicated at different times during the cAMP signaling response. cAMP stimulation of intact cells led to a transient activation of adenylate cyclase, which was blocked if 10(-4) M NaN3 was added with the stimulus. During responses elicited by 10(-6) M cAMP, 10(-8) M cAMP, and an increment in cAMP from 10(-8) M to 10(-7) M, the rate of cAMP secretion was proportional to the intracellular cAMP concentration. Removal of a 10(-6) M cAMP stimulus 2 min after the initiation of the response led to a precipitous decline in intracellular cAMP. This decline was more rapid than could be accounted for by secretion alone, suggesting intracellular phosphodiesterase destruction of newly synthesized cAMP. Employing these data and a simple rate equation, estimates of the time-course of the transient activation of adenylate cyclase and the rate constants for cAMP secretion and intracellular phosphodiesterase activity were obtained. The calculated rate of cAMP synthesis rose for approximately 1 to 2 min, peaked, and declined to approach prestimulus levels after 3 to 4 min. This time-course agreed qualitatively with direct measurements of the time-course of activation, indicating that the activation of adenylate cyclase is a major in determining the time-course of the cAMP secretion response.

scholarly journals Cyclic 3', 5'-AMP relay in Dictyostelium discoideum: adaptation is independent of activation of adenylate cyclase.

1983 ◽  
Vol 97 (1) ◽  
pp. 173-177 ◽  
Author(s):  
A Theibert ◽  
P N Devreotes
Keyword(s):  
Adenylate Cyclase ◽  
Dictyostelium Discoideum ◽  
Time Course ◽  
Initial Response ◽  
Activation Process ◽  
Surface Receptors ◽  
High Affinity ◽  
Camp Synthesis ◽  
Time Period ◽  
Rapid Activation

In Dictyostelium discoideum, binding of cAMP to high affinity surface receptors leads to a rapid activation of adenylate cyclase followed by subsequent adaptation within several minutes. The rate of secretion of [ 3H ]cAMP, which reflects the state of activation of the enzyme, was measured. Caffeine noncompetitively inhibited the response to cAMP. Inhibition was rapidly reversible and pretreatment of cells with caffeine for up to 22 min had little effect on the subsequent responsiveness to cAMP. However, cells pretreated with caffeine plus cAMP for greater than or equal to 8 min did not respond when caffeine was removed and the same concentration of cAMP was applied. The following observations indicate that both adaptation and deadaptation to cAMP occurred to the same extent and at the same rate whether or not cAMP synthesis was inhibited. First, when cells were pretreated with 10(-9)-10(-6) M cAMP in the presence or absence of caffeine and the stimulus was switched to a saturating dose of cAMP, the response to the increment was the same whether or not the initial response was blocked. Second, cells progressively lost responsiveness to 10(-6) M cAMP as pretreatment with 10(-6) M cAMP plus caffeine was extended from 0 to 8 min with the same time course as for those pretreated with 10(-6) M cAMP alone. Third, cells which were adapted in the presence of caffeine and cAMP deadapted within the same time period as controls when cAMP was removed. These observations demonstrate that while some part of the activation process is inhibited by caffeine the adaptation process is unaffected. Our conclusion is that adaptation does not depend on the activation of adenylate cyclase.

scholarly journals Studies on the time course and rate-limiting steps in the activation of adenylate cyclase in rat liver by cholera toxin

1978 ◽  
Vol 173 (1) ◽  
pp. 59-64 ◽  
Author(s):  
J Fischer ◽  
T R Kohler ◽  
L G Lipson ◽  
J Flores ◽  
P A Witkum ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Adenylate Cyclase ◽  
Cholera Toxin ◽  
Rat Liver ◽  
Time Course ◽  
Intact Cell ◽  
Intact Cells ◽  
Maximal Stimulation ◽  
Rate Limiting

Cholera toxin stimulates adenylate cyclase in rat liver after intravenous injection. The stimulation follows a short latent period of 10min, and maximum stimulation was attained at 120min. Half-maximal stimulation was achieved at 35min. In contrast with this lengthy time course in the intact cell, adenylate cyclase in broken-cell preparations of rat liver in vitro were maximally stimulated by cholera toxin (in the presence of NAD+) in 20min with half-maximal stimulation in 8min. Binding of cholera toxin to cell membranes by the B subunits is followed by translocation of the A subunit into the cell or cell membrane, and separation of the A1 polypeptide chain from the A2 chain by disulphide-bond reduction, and finally activation of adenylate cyclase by the A1 chain and NAD+. As the binding of cholera toxin is rapid, two possible rate-limiting steps could be the determinants of the long time course of action. These are translocation of the A1 chain from the outside of the cell membrane to its site of action (this includes the time required for separation from the whole toxin) or the availability of NAD+ for activation. When NAD+ concentrations in rat liver were elevated 4-fold, by the administration of nicotinamide, no change in the rate of activation of adenylate cyclase by cholera toxin was observed. Thus the intracellular concentration of NAD+ is not rate-limiting and the major rate-limiting determinant in intact cells must be between the time of toxin binding to the cell membrane and the appearance of subunit A1 at the enzyme site.

scholarly journals Induction of tyrosine aminotransferase in H-35 hepatoma cells by cAMP captured in phospholipid vesicles.

1981 ◽  
Vol 88 (1) ◽  
pp. 89-95 ◽  
Author(s):  
J A Culpepper ◽  
A Y Liu
Keyword(s):  
Cyclic Nucleotide ◽  
Lipid Vesicles ◽  
Tyrosine Aminotransferase ◽  
Hepatoma Cells ◽  
Receptor Protein ◽  
Regulatory Subunit ◽  
Phospholipid Vesicles ◽  
Intracellular Camp ◽  
Intact Cells ◽  
Relationship Of

The uptake, metabolism, and action of cAMP, captured within phospholipid vesicles, in H-35 hepatoma cells were studied. Sonication of lipids in buffer containing cAMP resulted in the formation of 300-A unilamellar lipid vesicles, capturing cAMP in the internal aqueous cavity. Incubation of H-35 hepatoma cells with vesicles containing cAMP (vesicle-cAMP) resulted in rapid incorporation of the vesicle content; apparent saturation of uptake was reached after approximately 30 min of incubation at 37 degrees C. Uptake of vesicle-cAMP was linear over a 10-fold vesicle concentration range. Pretreatment of cells with combined inhibitors of glycolysis and respiration inhibited vesicle uptake by 27%, suggesting vesicle fusion with the cell membrane as a predominant pathway of vesicle uptake. Studies on the metabolism of incorporated cAMP indicated that greater than 50% of the cell-associated radioactivity, derived from vesicle-[3H]cAMP, was preserved as cAMP at the end of a 20-min incubation at 37 degrees C. The incorporation of vesicle-cAMP by H-35 hepatoma cells resulted in increased tyrosine aminotransferase (TAT) activity. The concentration of vesicle-cAMP needed to produce a half-maximal increase in TAT activity was 10 microM, approximately two orders of magnitude lower than that of exogenously added dbcAMP. cAMP was ineffective when added extracellularly. The kinetic relationship of the cAMP-induced increase in TAT activity and the binding of cAMP to its receptor protein, in intact H-35 cells, was examined using vesicle-trapped 8-N3-cAMP, a photoaffinity labeling analogue of cAMP. Incubation of H-35 hepatoma cells with vesicle-8-N3-cAMP resulted in increased TAT activity, preceded by the binding of 8-N3-cAMP to the regulatory subunit of type II cAMP-dependent protein kinase. The use of lipid vesicles provides a means of modulating intracellular cAMP concentration without adding cyclic nucleotide in the millimolar concentration range to the extracellular medium. The increased efficiency of intracellular delivery of cyclic nucleotide with retention of biological activity, provides a useful technique in examining the relationship of occupancy of specific cAMP-receptor protein(s) and the occurrence of a cAMP-mediated biological response in intact cells.

scholarly journals Cyclic 3', 5'-AMP relay in dictyostelium discoideum. IV. Recovery of the cAMP signaling response after adaptation to cAMP

1980 ◽  
Vol 86 (2) ◽  
pp. 545-553 ◽  
Author(s):  
M Dinauer ◽  
TL Steck ◽  
P Devreotes
Keyword(s):  
Time Course ◽  
Recovery Period ◽  
Camp Signaling ◽  
Intracellular Camp ◽  
Surface Receptors ◽  
First Order ◽  
Cellular Processes ◽  
First Order Kinetics ◽  
Rate Limiting Step ◽  
Rate Limiting

In dictyoselium discoideum, an increase in extracellular cAMP activates adenylate cyclase, leading to an increase in intracellular cAMP and the rate of cAMP secretion. Cells adapt to any constant cAMP stimulus after several minutes, but still respond to an increase in the concentration of the stimulus. We have now characterized the decay of adaptation (deadaptation) after the removal of cAMP stimuli. Levels of adaptation were established by the perfusion of [(3)H]adenosine-labeled amoebae with a defined cAMP stimulus. After a variable recovery period, the magnitude of the signaling response to a second stimulus was measured; its attenuation was taken as a measure of residual adaption to the first stimulus. The level of adaptation established by the first stimulus depended on both its magnitude and duration. Deadaptation began as soon as the first stimulus was removed. The magnitude of the response to the second stimulus increased with the recovery time in a first-order fashion, with a t(1/2)=3-4 min for stimuli of 10(-8) M to 10(-5) M cAMP. Responses to test stimuli, although reduced in magnitude, had an accelerated time-course when they closely followed a prior response that had not completely subsided. This effect is called priming; we believe it reveals a reversible, rate-limiting step that modulates the onset and termination of the signaling responses of amoebae that have not recently responded to a cAMP stimulus. We have suggested that the cAMP signaling response is controlled by two antagonistic cellular processes, excitation and adaptation. The data reported here imply that both the rate of rise in the adaptation process and the final level reached depend on the occupancy of cAMP surface receptors and that the decay of adaptation when external cAMP is removed proceeds with first-order kinetics.

scholarly journals Novel bradykinin signalling events in PC-12 cells: stimulation of the cAMP pathway leads to cAMP-mediated translocation of protein kinase Cε

1997 ◽  
Vol 327 (1) ◽  
pp. 147-154 ◽  
Author(s):  
Angela GRANESS ◽  
Antje ADOMEIT ◽  
Beate LUDWIG ◽  
Wolf-Dieter MÜLLER ◽  
Roland KAUFMANN ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Adenylate Cyclase ◽  
Time Course ◽  
Inositol Phosphate ◽  
Fold Increase ◽  
Intracellular Camp ◽  
Camp Accumulation ◽  
Pc 12 Cells ◽  
Camp Pathway ◽  
Stimulation Of

In the rat pheochromocytoma cell line PC-12, bradykinin (BK) stimulated phosphatidylinositol hydrolysis by 4–5-fold and, additionally, intracellular cAMP accumulation by approx. 1.6-fold. EC50 values for BK were 3 nM and 2 nM respectively. The BK-induced increase in cAMP accumulation was paralleled by a 1.6-fold increase in protein kinase A (PKA) activity. The time course of BK-stimulated inositol phosphate formation was rapid (t1/2 < 1 min), whereas the BK-induced cAMP accumulation was lagging (t1/2 approx. 6 min). The effect of BK on the cAMP pathway was independent of pertussis toxin, excluding an indirect stimulation of adenylate cyclase via βγ-complexes from Gi or Go proteins. Two different protein kinase C (PKC) inhibitors, bisindolylmaleimide and Ro 31-820, failed to prevent BK-induced cAMP accumulation, and exclude PKC as mediator of BK action on adenylate cyclase. In contrast, the stimulatory effect of BK on cAMP accumulation was completely abolished by two calmodulin antagonists, chlorpromazine and ophiobolin, suggesting an indirect, Ca2+/calmodulin-mediated effect of BK on the cAMP pathway. In addition, exposure of PC-12 cells to BK resulted in a translocation of the PKC isoforms α, δ, ϵ and ζ displaying different kinetics. The BK-induced translocations of the PKCs α and δ were rapid and biphasic, whereas the PKCs ϵ and ζ revealed a slower and slightly transient translocation in response to BK. The BK-elicited translocation of PKCϵ, but not that of the PKCs α, δ and ζ, was prevented by two different inhibitors of adenylate cyclase, 2′,5′-dideoxyadenosine and MDL-12,330A, as well as the PKA inhibitor adenosine 3′:5′-monophosphothioate. These findings suggest that the BK-induced translocation of novel (n)PKCϵ is mediated via the cAMP pathway. Since nPKCϵ appears to regulate neurite outgrowth in PC-12 cells [Hundke, McMahon, Dadgar and Messing (1995) J. Biol. Chem. 270, 30134–30140] our results provide evidence for a novel signalling mechanism that might be involved in BK-induced neuronal differentiation of PC-12 cells.

scholarly journals Cyclic 3', 5'-AMP relay dictyostelium discoideum. V. Adaptation of the cAMP signaling response during cAMP stimulation

1980 ◽  
Vol 86 (2) ◽  
pp. 554-561 ◽  
Author(s):  
M Dinauer ◽  
TL Steck ◽  
P Devreotes
Keyword(s):  
Adenylate Cyclase ◽  
Test Stimulus ◽  
Dictyostelium Discoideum ◽  
Time Course ◽  
Intracellular Camp ◽  
Perfusion Technique ◽  
Adaptation Mechanism ◽  
Cellular Processes ◽  
Extracellular Camp ◽  
Camp Stimulation

In dictyostelium discoideum, extracellular cAMP activates adenylate cyclase, which leads to an increase in intracellular cAMP and the rate of cAMP secretion. The signaling response to a constant cAMP stimulus is terminated after several minutes by an adaptation mechanism. The time- course of adaptation stimuli of 10(-6) or 10(-7) M cAMP was assessed. We used a perfusion technique to deliver defined cAMP stimuli to [(3)H]adenosine-labeled amoebae and monitored their secretion of [(3)H]cAMP. Amoebae were pretreated with 10(-6) or 10(-7) M cAMP to periods of 0.33-12 minutes, and then immediately given test stimuli of 10(-8) M to 2.5 x 10(-7) M cAMP. The response to a given test stimulus was progressively attenuated and finally extinguished as the duration of the pretreatment stimulus increased. During concentration of the test stimulus. The responses to test stimuli of 10(-8), 5 x 10(-8), 10(-7), or 2.5 x 10(-7) M cAMP were extinguished after approximately 1, 2.25,2.5, and 10 min, respectively. 1.5 min of stimulation with 10(-7) M cAMP was necessary to extinguish the response of a test stimulus of 10(-8) M cAMP. Our data suggest that adaptation begins within 20 s of stimulation, rises rapidly for approximately 2.5 min, and reaches a plateau after approximately 10 min. The absolute rate of rise was faster during pretreatment with 10(-6) than with 10(-7) M cAMP. These results support a working hypothesis in which the occupancy of surface cAMP receptors leads to changes in two opposing cellular processes, excitation and adaptation, that control the activity of D. discoideum adenylate cyclase.

scholarly journals The effect of intracellular calcium ions on adrenaline-stimulated adenosine 3′:5′-cyclic monophosphate concentrations in pigeon erythrocytes, studied by using the ionophore A23187

1976 ◽  
Vol 158 (2) ◽  
pp. 211-221 ◽  
Author(s):  
A K Campbell ◽  
K Siddle
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Time Course ◽  
Ionophore A23187 ◽  
Atp Content ◽  
Bivalent Cation ◽  
Intact Cells ◽  
Maximum Inhibition ◽  
Partial Reversal ◽  
Stimulation Of

1. The bivalent cation ionophore A23187 was used to increase the intracellular concentration of Ca2+ in pigeon erythrocytes to investigate whether the increase in cyclic AMP content caused by adrenaline might be influenced by a change in intracellular Ca2+ in intact cells. 2. Incubation of cells with adrenaline, in the concentration range 0.55--55 muM, resulted in an increase in the concentration of cyclic AMP over a period of 60 min. The effect of adrenaline was inhibited by more than 90% with ionophore A23187 (1.9 muM) in the presence of 1 mM-Ca2+. This inhibition could be decreased by decreasing either the concentration of the ionophore or the concentration of extracellular Ca2+, and was independent of the concentration of adrenaline. 3. The effect of ionophore A23187 depended on the time of incubation. Time-course studies showed that maximum inhibition by ionophore A23187 was only observed when the cells were incubated with the ionophore for at least 15 min before the addition of adrenaline. 4. The inhibition by ionophore A23187 depended on the concentration of extracellular Ca2+. In the absence of Mg2+, ionophore A23187 (1.9 muM) inhibited the effect of adrenaline by approx. 30% without added Ca2+, by approx. 66% with 10 muM-Ca2+ and by more than 90% with concentrations of added Ca2+ greater than 30 muM. However, even in the presence of EGTA [ethanedioxybis(ethylamine)tetra-acetate](0.1--10 mM), ionophore A23187 caused an inhibition of the cyclic AMP response of at least 30%, which may have been due to a decrease in cell Mg2+ concentration. 5. The addition of EGTA after incubation of cells with ionophore A23187 resulted in a partial reversal of the inhibition of the effect of adrenaline. 6. Inclusion of Mg2+ (2 mM) in the incubation medium antagonized the inhibitory action of ionophore A23187. This effect was most marked when the ionophore A23187 was added to medium containing Mg2+ before the addition of the cells. 7. The cellular content of Mg2+ was decreased by approx. 50% after 20 min incubation with ionophore A23187 (1.9 muM) in the presence of Ca2+ (1 mM) but no Mg2+. When Mg2+ (2 mM) was also present in the medium, ionophore A23187 caused an increase of approx. 80% in cell Mg2+ content. Ionophore A23187 had no significant effect on cell K+ content. 8. Ionophore A23187 caused a decrease in cell ATP content under some conditions. Since effects on cyclic AMP content could also be shown when ATP was not significanlty lowered, it appeared that a decrease in ATP in the cells could not explain the effect of ionophore A23187 on cyclic AMP. 9. Ionophore A23187 (1.9 muM), with 1 mM-Ca2+, did not enhance cyclic AMP degradation in intact cells, suggesting that the effect of ionophore A23187 on cyclic AMP content was mediated through an inhibition of adenylate cyclase rather than a stimulation of cyclic AMP phosphodiesterase. 10. It was concluded that in intact pigeon erythrocytes adenylate cyclase may be inhibited by intracellular concentrations of Ca2+ in the range 1-10 muM.

scholarly journals CAP1, an Adenylate Cyclase-Associated Protein Gene, Regulates Bud-Hypha Transitions, Filamentous Growth, and Cyclic AMP Levels and Is Required for Virulence of Candida albicans

2001 ◽  
Vol 183 (10) ◽  
pp. 3211-3223 ◽  
Author(s):  
Yong-Sun Bahn ◽  
Paula Sundstrom
Keyword(s):  
Candida Albicans ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Germ Tube ◽  
Filamentous Growth ◽  
Tube Formation ◽  
Camp Signaling ◽  
Solid Media ◽  
Opportunistic Fungal Pathogen ◽  
Camp Levels

ABSTRACT In response to a wide variety of environmental stimuli, the opportunistic fungal pathogen Candida albicans exits the budding cycle, producing germ tubes and hyphae concomitant with expression of virulence genes, such as that encoding hyphal wall protein 1 (HWP1). Biochemical studies implicate cyclic AMP (cAMP) increases in promoting bud-hypha transitions, but genetic evidence relating genes that control cAMP levels to bud-hypha transitions has not been reported. Adenylate cyclase-associated proteins (CAPs) of nonpathogenic fungi interact with Ras and adenylate cyclase to increase cAMP levels under specific environmental conditions. To initiate studies on the relationship between cAMP signaling and bud-hypha transitions in C. albicans, we identified, cloned, characterized, and disrupted the C. albicans CAP1 gene. C. albicans strains with inactivated CAP1 budded in conditions that led to germ tube formation in isogenic strains withCAP1. The addition of 10 mM cAMP and dibutyryl cAMP promoted bud-hypha transitions and filamentous growth in thecap1/cap1 mutant in liquid and solid media, respectively, showing clearly that cAMP promotes hypha formation in C. albicans. Increases in cytoplasmic cAMP preceding germ tube emergence in strains having CAP1 were markedly diminished in the budding cap1/cap1 mutant. C. albicans strains with deletions of both alleles ofCAP1 were avirulent in a mouse model of systemic candidiasis. The avirulence of a germ tube-deficientcap1/cap1 mutant coupled with the role of Cap1 in regulating cAMP levels shows that the Cap1-mediated cAMP signaling pathway is required for bud-hypha transitions, filamentous growth, and the pathogenesis of candidiasis.

scholarly journals Complexing of the CD-3 subunit by a monoclonal antibody activates a microtubule-associated protein 2 (MAP-2) serine kinase in Jurkat cells

1989 ◽  
Vol 262 (2) ◽  
pp. 449-456 ◽  
Author(s):  
C Hanekom ◽  
A Nel ◽  
C Gittinger ◽  
A Rheeder ◽  
G Landreth
Keyword(s):  
T Cells ◽  
Time Course ◽  
Gel Filtration ◽  
Maximal Activity ◽  
Jurkat Cells ◽  
Serine Kinase ◽  
Transient Activation ◽  
Normal Human ◽  
Dose Dependent

Treatment of Jurkat T-cells with anti-CD-3 monoclonal antibodies resulted in the rapid and transient activation of a serine kinase which utilized the microtubule-associated protein, MAP-2, as a substrate in vitro. The kinase was also activated on treatment of Jurkat cells with phytohaemagglutinin, but with a different time course. The activation of the MAP-2 kinase by anti-CD-3 antibodies was dose-dependent, with maximal activity observed at concentrations of greater than 500 ng/ml. Normal human E-rosette-positive T-cells also exhibited induction of MAP-2 kinase activity during anti-CD-3 treatment. The enzyme was optimally active in the presence of 2 mM-Mn2+; lower levels of activity were observed with Mg2+, even at concentrations up to 20 mM. The kinase was partially purified by passage over DE-52 Sephacel with the activity eluting as a single peak at 0.25 M-NaCl. The molecular mass was estimated to be 45 kDa by gel filtration. The activation of the MAP-2 kinase was probably due to phosphorylation of this enzyme as treatment with alkaline phosphatase diminished its activity. These data demonstrate that the stimulation of T-cells through the CD-3 complex results in the activation of a novel serine kinase which may be critically involved in signal transduction in these cells.

scholarly journals PGE2-mediated inhibition of T cell p59fynis independent of cAMP

1999 ◽  
Vol 277 (2) ◽  
pp. C302-C309 ◽  
Author(s):  
Mashkoor A. Choudhry ◽  
Zulfiqar Ahmed ◽  
Mohammed M. Sayeed
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adenylate Cyclase ◽  
Protein Tyrosine Kinase ◽  
Kinase Activity ◽  
Prostaglandin E ◽  
Intracellular Camp ◽  
Sprague Dawley ◽  
Cell Functions ◽  
Camp Levels

We recently observed that prostaglandin E2(PGE2)-mediated suppression of T cell functions could result from an attenuation of p59fynprotein tyrosine kinase activity. The present study evaluated the effects of an adenylate cyclase agonist (forskolin) and antagonist (SQ-22536), as well as those of cAMP analogues (dibutyryl cAMP and 8-bromo- cAMP), on T cell p59fynkinase activity. The study allowed us to assess whether PGE2-mediated activation of adenylate cyclase by itself or the elevation in intracellular cAMP levels is an integral event in the modulation of anti-CD3-linked p59fynactivation in T cells. The experiments were carried out with splenic T cells from male Sprague-Dawley rats. A 30–50% suppression in the autophosphorylation and the kinase activity of p59fynin T cells incubated with PGE2or forskolin was observed. Pretreatment of T cells with SQ-22536 prevented significant PGE2-mediated inhibition of T cell p59fynkinase activity. In contrast, no change in p59fynautophosphorylation and kinase activity in T cells treated with cAMP analogues was observed. These data suggest that PGE2-mediated suppression of p59fynautophosphorylation and kinase activity in T cells is dependent on the activation of adenylate cyclase and independent of the elevation in cAMP levels.

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