Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A peptide-containing extract (PE) from Helix nervous system modifies the endogenous bursting pattern of electrical activity in Helix neurone F-1. This effect is similar to that induced in neuron F-1 by certain phosphodiesterase inhibitors and cAMP derivatives. The PE, and the vertebrate peptide hormones vasopressin and oxytocin, also cause an accumulation of cAMP in Helix ganglia in vitro. The factor in the PE which causes the cAMP accumulation is destroyed by Pronase, is lost on dialysis, and is stable to boiling. In all these respects it is identical to the factor which causes the change in neuronal electrical activity. The PE also stimulates adenylate cyclase activity in a crude membrane fraction prepared from Helix ganglion homogenates. This stimulation is abolished by prior dialysis of the PE, or pretreatment of the PE with pepsin, but is not affected by boiling of the PE. Pepsin-treated PE has no effect on electrical activity in neuron F-1. The adenylate cyclase-stimulating activity of the PE, like the factor which modifies neurone F-1 electrical activity, elutes in the void volume of a Sephadex G-10 column. The included volume of this column contains a factor which inhibits PE modification of neuronal electrical activity, and also inhibits both basal and PE-stimulated adenylate cyclase activity. The data are consistent with the possibility that cAMP mediates the effects of the PE on electrical activity in molluscan neurones.
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PMID:Modulation of electrical activity and cyclic nucleotide metabolism in molluscan nervous system by a peptide-containing nervous system extract. 20 Mar 7

Leukocyte extracts containing human transfer factor (TF) were fractionated by exclusion chromatography, and the active fraction (Sephadex G25, Fraction IIIa) was subjected to high pressure, reverse phase (HPRP) chromatography and enzymatic degradation. TF activity was assessed by the systemic transfer of dermal skin test reactivity from KLH-immunized donors to naive recipients. Preparative HPRP chromatography resolved Fraction IIIa into multiple chromophoric regions, two of which demonstrated transfer of KLH reactivity. Alkaline phosphatase treatment of Fraction IIIa converted the major ultraviolet-absorbing component, 5'-inosine monophosphate, to inosine and resulted in TF activity being restricted to one region. This HPRP region (R1A) contained less than 1% of the UV254 active material in Fraction IIIa but greater than 90% of the reactivity. The sensitivity of TF to pronase, proteinase K, phosphodiesterase I, and phosphodiesterase II was evaluated by inhibition of systemic transfer of KLH reactivity. Pronase and proteinase K destroyed systemic transfer activity and the pronase destruction could be inhibited with traysylol. Phosphodiesterase I, a 3' exonuclease, destroyed activity, whereas phosphodiesterase II, a 5' exonuclease, did not. The data are consistent with a phosphodiester-containing polypeptide in the structure of human TF for KLH reactivity.
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PMID:Human transfer factors: structural properties suggested by HPRP chromatography and enzymatic sensitivities. 44 71

Polyclonal antibodies to native alkaline phosphatase and to native 5'-nucleotide phosphodiesterase were found to strongly cross-react with both enzymes. The antibodies also cross-react with both denatured enzymes, with glycopeptides from 5'-nucleotide phosphodiesterase, and with the oligosaccharides remaining after Pronase E digestion of the phosphodiesterase. They do not cross-react with either enzyme after their oligosaccharides have been modified or removed by periodate or trifluoromethanesulfonic acid treatment. Antibodies to denatured 5'-nucleotide phosphodiesterase do not bind to the native phosphodiesterase or alkaline phosphatase but do cross-react with denatured alkaline phosphatase even after removal or modification of the carbohydrate moieties. These results suggest that antibodies to denatured 5'-nucleotide phosphodiesterase may recognize amino acid sequence homology between alkaline phosphatase and 5'-nucleotide phosphodiesterase. However, antibodies to native enzymes apparently recognize cross-reactive determinants of the native enzymes which are carbohydrate in nature. This is the first report of antimammalian alkaline phosphatase antibodies which recognize the carbohydrate moieties of the enzyme.
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PMID:Alkaline phosphatase and 5'-nucleotide phosphodiesterase from bovine intestine are cross-reactive. 241 45

Phosphorylation of histone H1 occurs when spermatozoa of the sea urchin Strongylocentrotus purpuratus are treated with the macromolecular fraction of solubilized egg jelly. Phosphorylation is on serine residues in the N-terminal fragment of H1 bisected with N-bromosuccinimide. Phosphorylation is maximal by 4-8 min and dependent on Ca2+, but independent of Na+ or increased intracellular pH. Phosphorylation of H1 can be dissociated from the induction of the acrosome reaction. Only a fraction of the H1 molecules become phosphorylated upon treatment of sperm with egg jelly. The amount of phosphate per mole of H1 increases from 0.15 moles before jelly treatment to 0.46 moles after maximal phosphorylation. Phosphorylation of H1 occurs in a cAMP-dependent manner as indicated by the ability of the phosphodiesterase inhibitors IBMX and SQ20009 to induce H1 phosphorylation. This phosphorylation reaction can be blocked by digesting the sperm surface with Pronase, or preincubation of sperm in wheat germ agglutinin, showing that a ligand in egg jelly must interact with a sperm surface receptor to activate the kinase phosphorylating H1.
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PMID:Phosphorylation of sperm histone H1 is induced by the egg jelly layer in the sea urchin Strongylocentrotus purpuratus. 242 45

Resumption of meiosis in starfish oocytes is induced by 1-methyladenine (1-MeAde) produced by ovarian follicle cells under the influence of a gonad-stimulating substance (GSS). It has also been reported that concanavalin A (Con A) and two serine proteolytic enzymes (trypsin and Pronase) can stimulate 1-MeAde production. This study was undertaken to determine if 1-MeAde production induced by these compounds is mediated through elevation of cAMP in starfish (Asterina pectinifera) follicle cells. GSS at a concentration of 0.1 mg/ml significantly stimulated 1-MeAde accumulation in extracellular medium after 1-2 hr of follicle cell incubations. GSS also caused a four- to fivefold increase in intracellular levels of cAMP. The continuous presence of GSS was required for the maintenance of elevated levels of cAMP and 1-MeAde. Basal levels of intracellular cGMP were only about 20% of those of cAMP and were not influenced by treatment with GSS. At 1 mM, 3-isobutyl-1-methylxanthine (IBMX), a potent phosphodiesterase inhibitor, stimulated both 1-MeAde and cAMP production in a concentration-dependent manner. Con A and two serine proteases also raised both cAMP and 1-MeAde production. Con A-induced (1.0 mg/ml) increases in cAMP and 1-MeAde were greater than the response to GSS (0.1 mg/ml) and were completely suppressed by treatment with alpha-methyl-D-mannoside (10 mM), a competitive inhibitor of Con A. These results strongly suggest that cAMP is a second messenger in the production of 1-MeAde by starfish ovarian follicle cells.
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PMID:Mediation of cyclic adenosine 3',5'-monophosphate in 1-methyladenine production by starfish ovarian follicle cells. 255 21

Purified calmodulin-stimulated cyclic nucleotide phosphodiesterase from brain, a homodimer of 59-kDa subunits, was activated by limited proteolysis with trypsin, alpha-chymotrypsin, Pronase, or papain and could not be further stimulated by addition of Ca2+ and calmodulin. Proteolysis increased Vmax and had little effect on the Km for cGMP. Treatment with alpha-chymotrypsin in the presence of ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) produced, sequentially, 57- and 45-kDa peptides from the bovine and 55-, 53-, and 38-kDa peptides from the ovine enzyme. This protease-treated phosphodiesterase exhibited a Stokes radius of 3.9 nm and an S20,w value of 4.55; comparison with the hydrodynamic properties observed for native enzyme (4.3 nm, 5.95 S) strongly suggests a dimeric protein of Mr approximately 80,000-90,000. The proteolyzed species does not interact significantly with calmodulin immobilized on agarose, nor does it show complex formation with 2-dimethylaminonaphthalene-1-sulfonyl-calmodulin even at micromolar concentrations of protein. Proteolysis, in the presence of calmodulin plus Ca2+, fully activated phosphodiesterase, producing the same intermediate peptides; however, final peptides from the bovine and ovine enzymes were 47 and 42 kDa, respectively, indicating a new, specific conformation of the enzyme. When EGTA was added to such incubations, these peptides were cleaved to those of the size seen when proteolysis was carried out entirely in the presence of EGTA. The initial rate of activation was increased by the presence of Ca2+ and calmodulin, suggesting that, in complex, phosphodiesterase exhibits a site with increased susceptibility to proteolysis. Since calmodulin can still interact with a fully activated form of the enzyme, it appears that retention of calmodulin binding can occur concomitantly with damage to that portion of the phosphodiesterase molecule responsible for suppression of its basal catalytic activity.
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PMID:Proteolytic activation of calmodulin-dependent cyclic nucleotide phosphodiesterase. 299 Dec 33