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Query: HUMANGGP:030741 (calmodulin-dependent phosphodiesterase)
 89 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A model for the activation of phosphodiesterase by calmodulin based on a conversion of inactive dimers to active monomers, derived from radiation inactivation studies J. Biol. Chem. (1981) 256, 11351-11355 has been re-examined using a simple probability argument. We conclude that the original model is not supported by the radiation inactivation studies, since our analysis of this model would predict that the rate of radiation inactivation of calmodulin-dependent phosphodiesterase activity be exactly twice that for the decay in total activity in marked contrast with the results obtained.
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PMID:The substructure of phosphodiesterase as established by radiation inactivation. A reinterpretation of results. 629 77

The interaction of aluminum ions with bovine brain calmodulin has been examined by fluorescence spectroscopy, circular dichroic spectrophotometry and equilibrium dialysis, and by the calmodulin-dependent activation of 3',5'-cyclic nucleotide phosphodiesterase. These experiments show that aluminum binds stoichiometrically and cooperatively to calmodulin. Binding of aluminum at a molar ratio of 2:1 to calmodulin suffices to induce a major structural change. Estimates from spectroscopic data indicate that the binding affinity for the first mol of aluminum bound to the protein is about one order of magnitude stronger than that of calcium to its comparable site. These estimates agree with a dissociation constant of 0.4 microM derived from equilibrium dialysis experiments. Interaction of aluminum with calmodulin induces a helix-coil transition and enhances the hydrophobic surface area much more than calcium does. A molar ratio of 4:1 for [aluminum]/[calmodulin] is sufficient to block completely the activity of the calcium-calmodulin-dependent phosphodiesterase. Highly hydrated aluminum ions apparently promote solvent-rich, disordered polypeptide regions in calmodulin which, in turn, profoundly influence the protein's flexibility.
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PMID:Aluminum interaction with calmodulin. Evidence for altered structure and function from optical and enzymatic studies. 629 65

We have isolated two Ca2+-binding proteins from squid optic lobes, each of which is also able to bind phenothiazines in a Ca2+-dependent manner. These proteins have each been purified and partly characterized. One of the proteins corresponds to calmodulin, in that it has a similar amino acid content to bovine brain calmodulin, including a single residue of trimethyl-lysine, it co-migrates with bovine calmodulin both on alkaline-urea- and on sodium dodecyl sulphate (SDS)/polyacrylamide-gel electrophoresis, and will activate calmodulin-dependent phosphodiesterase. The second protein has the same subunit molecular weight as calmodulin, as determined by SDS/polyacrylamide-gel electrophoresis, Mr 17 000, but migrates more slowly than this protein on alkaline-urea-gel electrophoresis. It has an amino acid composition distinct from calmodulin, containing no trimethyl-lysine, its CNBr fragments migrate on alkaline gels in a pattern distinct from those of calmodulin and it shows little ability to activate phosphodiesterase. The u.v.-absorption spectra of the proteins indicate the absence of tryptophan and the presence of a high phenylalanine/tyrosine ratio in each. Both proteins also bind 3-4 calcium ions/mol at 0.1 mM-free Ca2+ and each binds chlorpromazine in a Ca2+-dependent manner.
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PMID:Two low-molecular-weight Ca2+-binding proteins isolated from squid optic lobe by phenothiazine--Sepharose affinity chromatography. 630 66

The regulatory role of calcium ion was investigated in isolated 10-day-old corpora lutea incubated in vitro. The corpora lutea were induced in immature rats by a single injection of PMSG (15 i.u.) on day 30. We examined the effect of various incubation conditions on the increase (about 7-fold) in cyclic AMP (cAMP) concentration by LH (5 micrograms/ml) and its reversal by PGF2 alpha (10 microM). In calcium-free medium (+0.5 mM EGTA) the stimulation by LH was only slightly impaired, and PGF2 alpha was fully effective in suppressing it. Similarly, both LH and PGF2 alpha acted normally in the presence of 100 microM verapamil, a blocker of calcium uptake. Trifluoperazine (TFP, 3-300 microM) a potent inactivator of calmodulin, did not interfere with the action of PGF2 alpha. The effect of LH was increased by TFP (30 and 300 microM); this was probably due to inhibition of calmodulin-dependent phosphodiesterase, since the increase of the response to LH by IBMX (0.5 mM) plus TFP (30 microM) was similar to that by IBMX alone. Finally, the uptake of radioactive calcium was not increased by PGF2 alpha in the absence or presence of LH. These results do not support the suggestion that calcium ion mediates the hormonal regulation of cAMP in the rat corpus luteum.
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PMID:The role of calcium ion in luteal function in the rat. 631 Feb 58

Carboxylmethylation of several preparations of cAMP phosphodiesterase by the enzyme protein O- carboxylmethyltransferase and S-adenosylmethionine reduces the extent to which the enzyme was activated by native calmodulin. In contrast, carboxylmethylation of calmodulin produced only a slight reduction in the ability of calmodulin to activate cAMP phosphodiesterase. The effect of carboxylmethylation of calmodulin was most prominent at subsaturating calmodulin concentrations, whereas the reduction in the activation of carboxylmethylated cAMP phosphodiesterase was independent of calmodulin concentration. Kinetics and stoichiometric analysis of calmodulin carboxylmethylation indicated that less than 5% of calmodulin was methylated and that the Km of protein O- carboxylmethyltransferase for calmodulin was approximately 350 microM. The extent of calmodulin carboxylmethylation was not affected by either EGTA or Ca2+. When homogeneous bovine brain phosphodiesterase was carboxylmethylated , a rapid decrease in calmodulin-induced stimulation was noted, occurring within 30 s of incubation. Acidic sodium dodecyl sulfate-gel electrophoresis of bovine brain phosphodiesterase revealed a major band of 60,000 daltons which contained radio-activity after carboxylmethylation . Stoichiometric analysis revealed that approximately 20% of the phosphodiesterase was carboxylmethylated . Thus, although calmodulin can serve as a substrate for carboxylmethylation , it appears that carboxylmethylation has a greater effect on calmodulin-dependent phosphodiesterase activity when the target enzyme, rather than calmodulin, is carboxylmethylated .
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PMID:Carboxylmethylation of phosphodiesterase attenuates its activation by ca2+-calmodulin. 632 88

A low molecular weight protein of about 17 000 as determined by SDS-polyacrylamide gel electrophoresis has been isolated from cilia and cell bodies, respectively, from Paramecium tetraurelia (wildtyp 51s). This protein has been identified as calmodulin by various properties previously ascribed to calmodulin from other vertebrate and invertebrate systems. These properties are heat stability, electrophoretic mobility and its ability to activate in the presence of calcium a calmodulin-dependent phosphodiesterase from pig brain. Calmodulin is present in rather high amounts in cell bodies (75 micrograms/g) and also in isolated cell-free cilia (up to 50 micrograms/g). Its presence in cilia suggests a role in the control of ciliary activity.
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PMID:Calcium receptor protein calmodulin isolated from cilia and cells of Paramecium tetraurelia. 723 39

The second messenger molecules cAMP and Ca2+ regulate a large number of eukaryotic cellular events. cAMP acts on protein kinases, and Ca2+ works through a ubiquitous calcium-binding protein, calmodulin. The 2 systems are not independent, however, but interact in several important fashions. These interactions can be demonstrated by calmodulin-dependent phosphodiesterase. The bovine heart calmodulin-dependent phosphodiesterase can be phosphorylated by cAMP-dependent protein kinase, resulting in a decrease in the enzyme's affinity for calmodulin. The phosphorylation of calmodulin-dependent phosphodiesterase is blocked by Ca2+ and calmodulin, and reversed by the calmodulin-dependent phosphatase (calcineurin). The dephosphorylation is accompanied by an increase in the affinity of the phosphodiesterase for calmodulin. Results from this study suggest that the activity of this phosphodiesterase is precisely regulated by cross-talk between Ca2+ and cAMP signalling pathways.
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PMID:Molecular interaction between cAMP and calcium in calmodulin-dependent cyclic nucleotide phosphodiesterase system. 798

Two forms of phosphodiesterase (F1 and F2) with different regulatory properties have been isolated from the soluble fraction of human brain cortex. F1 is the Ca(2+)-calmodulin-dependent phosphodiesterase and its activity is inhibited by calmodulin antagonists (W-7, TFP, tamoxifen) via a mechanism typical for the majority of Ca(2+)-calmodulin-dependent enzymes. F2 is activated by micromolar concentrations of cGMP (7-14-fold) and by Ca2+ ions (1.5-3-fold) in the absence of exogenous calmodulin. F2 contains a tightly bound Ca(2+)-binding component (apparently calmodulin) which does not dissociate from the enzyme in the presence of EGTA. The mechanism of calmodulin antagonists action on F2 is different from that for F1.
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PMID:[Ca2+-dependent regulation of cGMP-stimulated phosphodiesterase from the soluble fraction of the human brain]. 807 51

Based on their relative abundance and regulation by Ca2+ and by phosphorylation in vitro, it is thought that the Ca2+/calmodulin-dependent phosphodiesterases (CaM-PDEs) are important modulators of cyclic nucleotide function in the brain. Two of the most abundant CaM-PDEs in the brain are the 61 kDa and 63 kDa isozymes. In this study, the regional and cellular expression of mRNA encoding these two different isoforms in mouse brain has been determined by in situ hybridization. The 63 kDa CaM-PDE mRNA has a wide-spread but uneven distribution. Very strong hybridization signals are present in the caudate-putamen, nucleus accumbens, olfactory tubercle, and dentate gyrus of the hippocampus. Somewhat lesser amounts of 63 kDa CaM-PDE mRNA are present in the olfactory bulb and piriform cortex. Weaker but still easily discernible hybridization signals are seen in several layers of the cerebral cortex, CA1 and CA3 regions of the hippocampus, amygdaloid nuclear complex, thalamus, hypothalamus, midbrain, brainstem, cerebellum, and spinal cord. A weak hybridization signal was detected in the globus pallidus of the basal ganglia. In general, the distribution of the 63 kDa CaM-PDE is very similar to that of dopamine receptors, suggesting that it may modulate dopamine function. In contrast, the 61 kDa CaM-PDE mRNA has a more limited and much different distribution, with the highest level of expression in the cerebral cortex and in the pyramidal cells of the hippocampus. A moderate hybridization signal was detected in the medial habenula and amygdaloid nuclear complex. In addition, small subsets of neurons in several other regions showed specific hybridization. Both PDE mRNAs appear to be localized exclusively in neuronal cell bodies. Their distinct distribution suggests important but different physiological roles for these two isozymes in the regional regulation of cyclic nucleotides in the CNS. Since these two isozymes are differentially phosphorylated by cAMP-dependent and Ca2+/CaM-dependent protein kinases, the differential expression also provides a potential mechanism by which these PDEs can differentially regulate cAMP and cGMP in different brain areas. The high expression levels in specific subsets of neurons also suggest that agents increasing Ca2+ in these neurons will increase the rate of cyclic nucleotide degradation.
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PMID:Differential expression of the 61 kDa and 63 kDa calmodulin-dependent phosphodiesterases in the mouse brain. 812 Jun 37

Bovine brain contains two calmodulin-dependent phosphodiesterase kinases which are separated on Sephacryl S-300 column. One of these kinases has been purified to homogeneity and shown to belong to the calmodulin-dependent protein kinase II family. Phosphorylation of the 63 kDa phosphodiesterase by this purified protein kinase results in the incorporation of 1.0 mol phosphate per mol subunit and an accompanying increase in Ca2+ concentrations required for the phosphodiesterase activation by calmodulin. The protein kinase undergoes autophosphorylation to incorporate 1.0 mol phosphate per mol of subunit of the enzyme and the autophosphorylated enzyme is active, independent of the presence of Ca2+. The autophosphorylation reaction as well as the protein kinase reaction are rendered Ca2+ independent in less than 15 seconds when approximately one mol phosphate per mol protein kinase is incorporated. The result suggests that activation of phosphodiesterase phosphorylation reaction may occur prior to the activation of phosphodiesterase and phosphatase during a cell Ca2+ flux via the protein kinase autophosphorylation mechanism.
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PMID:Purification and characterization of bovine brain calmodulin-dependent protein kinase. II. The significance of autophosphorylation in the regulation of 63 kDa calmodulin-dependent cyclic nucleotide phosphodiesterase isozyme. 823 47


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