Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.3.16 (calcineurin)
17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulatory subunit of type I cAMP-dependent protein kinase (RI) from rabbit skeletal muscle inhibited the activity of a low molecular weight phosphoprotein phosphatase. The inhibition was concentration and time dependent. A maximum inhibition, about 70%, was observed at 2 microM of RI with an apparent Ki of 0.8 microM. Inhibition was associated with a decrease in Vmax with no change in Km for substrate, phosphorylase a. On the other hand, cAMP-dependent protein kinase holoenzyme or its catalytic subunit was without any effect. The inhibition of phosphoprotein phosphatase by RI may be of physiological significance since the dissociation of cAMP-dependent protein kinase by cAMP would result in a simultaneous increase in the phosphorylation and decrease in the dephosphorylation rates of target proteins.
...
PMID:Inhibitory effect of the regulatory subunit of type I cAMP-dependent protein kinase on phosphoprotein phosphatase. 283 51

Studies were performed to determine if the Na+-H+ exchanger, solubilized from renal brush border membranes from the rabbit and assayed in reconstituted artificial proteoliposomes, could be regulated by cAMP-dependent protein kinase. Octyl glucoside solubilized renal apical membrane proteins from the rabbit kidney were phosphorylated by incubation with ATP and highly purified catalytic subunit of cAMP-dependent kinase. 22Na+ uptake was determined subsequently after reconstitution of the proteins into proteoliposomes. cAMP-dependent protein kinase resulted in sustained protein phosphorylation and a concentration-dependent decrease in the amiloride-sensitive component of pH gradient-stimulated sodium uptake. The inhibitory effect of cAMP-dependent protein kinase demonstrated an absolute requirement for ATP and was blocked by the specific protein inhibitor of this kinase. cAMP-dependent protein kinase also inhibited 22Na+ uptake in the absence of a pH gradient (pHin 6.0, pHout 6.0) and the inhibitory effect was blocked by the specific inhibitor of the kinase. Solubilized membrane proteins exhibited little endogenous protein kinase or protein phosphatase activity. These studies indicate that Na+-H+ exchange activity of proteoliposomes reconstituted with proteins from renal brush border membranes is inhibited by phosphorylation of selected proteins by cAMP-dependent protein kinase. These findings also indicate that the regulatory components of the Na+-H+ exchanger remain active during the process of solubilization and reconstitution of renal apical membrane proteins.
...
PMID:Reconstitution of cAMP-dependent protein kinase regulated renal Na+-H+ exchanger. 283 85

A protein phosphatase which dephosphorylates phospholamban was purified from canine cardiac cytosol. Purification involved sequential chromatography on DEAE-Sephacel, polylysine-agarose, heparin-agarose, Mono Q HR 10/10, and Superose 6. The enzyme was composed of three subunits with Mr = 63,000, 55,000, and 38,000, and it could dephosphorylate the sites on phospholamban phosphorylated by either cAMP-dependent or calcium-calmodulin-dependent protein kinase. Phospholamban phosphatase activity was enhanced 12-, 9-, and 3-fold by the divalent cations Mg2+, Mn2+, and Ca2+, respectively. The phosphatase was inhibited by PPi, ATP, NaF, and Pi and the degree of inhibition was different with each compound. The substrate specificity of the purified phosphatase for cardiac phosphoproteins was determined using troponin I, phospholamban, and highly enriched sarcolemmal and sarcoplasmic reticulum preparations, phosphorylated by the cAMP-dependent protein kinase. The phosphatase exhibited the highest activity with phospholamban as substrate. Thus, dephosphorylation of phospholamban by this phosphatase may participate in regulation of sarcoplasmic reticulum function in cardiac muscle.
...
PMID:Purification and characterization of phospholamban phosphatase from cardiac muscle. 284 19

The ppd1 mutant of yeast, Saccharomyces cerevisiae, was isolated as a suppressor of the cyr2 mutation which caused alteration of the catalytic subunit of cAMP-dependent protein kinase. Three peaks of phosphoprotein phosphatase activity (peak I, II and III) were identified by DEAE-Sephacel chromatography of crude extracts of the wild-type strain. The ppd1 mutant was deficient in peak III phosphoprotein phosphatase activity. The peak III enzyme efficiently utilized the phosphorylated forms of NAD-dependent glutamate dehydrogenase and trehalase as substrate. The ppd1 mutation did not suppress the cyr1, CYR3 or ras1 ras2 mutations. The ppd1 locus was located on chromosome II and had identical characteristics with glc1. The ppd1 mutation suppressed the G1 arrest caused by nutritional limitation, but maintained sensitivity to mating pheromone. In diploids homozygous for the ppd1 mutation, no premeiotic DNA replication and commitment to intragenic recombination occurred and no spores were formed, suggesting that the accumulation of phosphorylated proteins in the absence of one of the phosphoprotein phosphatases is required for mitosis but not for the initiation of meiosis.
...
PMID:Isolation and characterization of a phosphoprotein phosphatase-deficient mutant in yeast. 285 99

Glycogen synthase a was purified from rabbit skeletal muscle by a procedure involving heparin-Sepharose chromatography. Glycogen synthase a was phosphorylated by the catalytic subunit of cAMP-dependent protein kinase to give synthase b1. Dephosphorylation and activation of synthase b1 was investigated using the catalytic subunits of protein phosphatase-1 and 2A. The dephosphorylation and activation of synthase b1 was biphasic with a larger rate constant for the initial phase. Analysis of tryptic phosphopeptides of glycogen synthase during the course of dephosphorylation revealed a faster initial phosphate release from site-2 by both phosphatases comparing to sites-1a and 1b. Ligand effects on synthase phosphatase reactions were also studied. Spermine was found to inhibit protein phosphatase-1 activity and to stimulate type-2A phosphatase using synthase b1 as substrate.
...
PMID:Activation/dephosphorylation of rabbit muscle glycogen synthase by the catalytic subunits of protein phosphatase-1 and 2A. 285 91

The protein phosphatases in rat liver cytosol, active on rat liver acetyl-CoA carboxylase (ACC) phosphorylated by casein kinase I, casein kinase II and the cAMP-dependent protein kinase, have been partially purified by anion-exchange and gel filtration chromatography. The major phosphatase activities against all three substrates copurify through fractionation and appear to be identical to protein phosphatases 2A1 and 2A2. No unique protein phosphatase active on 32P-ACC phosphorylated by the casein kinases was identified.
...
PMID:Protein phosphatases active on acetyl-CoA carboxylase phosphorylated by casein kinase I, casein kinase II and the cAMP-dependent protein kinase. 286 68

Acetyl-CoA carboxylase and its associated kinase have been purified to homogeneity from rat liver and, together with the catalytic subunit of liver protein phosphatase, used to study the effect of phosphorylation on the carboxylase activity. Phosphatase increases the carboxylase activity, whereas the kinase decreases it. A linear inverse relationship (correlation coefficient = 0.98) exists between phosphate incorporated by the kinase and the specific activity. The kinetics of activation by citrate show an increased Ka and a decreased Vmax for carboxylase preparations with increasing levels of phosphate. On this basis an enzymic test was devised for phosphate incorporated by the kinase. Thus the ratio of activities at 0 and 2 mM citrate is inversely proportional to the phosphate incorporated (correlation coefficient = -0.95), with 0.8 mol of P incorporated per mol of subunit decreasing the activity ratio from 0.5 to 0. This activity ratio method has an inherent internal control which makes it suitable for determining the level of protein-bound phosphate affecting the carboxylase activity in crude tissue extracts, and hence it should be useful for physiological studies. Tryptic maps of carboxylase labeled with radioactive phosphate by the carboxylase kinase indicate that the slightly less than 1 mol of P/mol of subunit is distributed equally between two peptides, whereas cAMP-dependent protein kinase phosphorylates these two sites and a third which may not affect activity.
...
PMID:Phosphorylation state of acetyl-coenzyme A carboxylase. I. Linear inverse relationship to activity ratios at different citrate concentrations. 287 33

The meiotic maturation of Xenopus laevis oocytes is induced in vitro by progesterone which interacts at the cell surface level. A cell-free membrane preparation (P-10,000) incorporated 32P from [gamma-32P]ATP, mostly into two proteins, Mr approximately 56,000 and approximately 48,000 (as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Progesterone, added in vitro, specifically inhibited the phosphorylation of the Mr approximately 48,000 protein (named p48). Half-maximal inhibition of p48 phosphorylation occurred with progesterone approximately 8 microM, in good correlation with hormone concentration inducing oocyte maturation. The effect was not due to stimulation of protein phosphatase activity. The potent maturation inducers testosterone and deoxycorticosterone also inhibited p48 phosphorylation, whereas biologically inactive steroids or cholesterol did not. p48 phosphorylation was not affected by cAMP, cGMP, polyamines, calmodulin, and phospholipids + diolein. EGTA had a stimulatory effect which was reversed by added Ca2+. The inhibitory effects of progesterone and Ca2+ were additive, suggesting two distinct sites of action. Phospho-p48 was not detected in yolk platelets, microsomes, and cytosol of oocytes. Contrary to p48 itself, the p48 kinase activity was loosely associated with P-10,000. Progesterone inhibited p48 phosphorylation produced by either cytosol or exogenous pure catalytic subunit of cAMP-dependent protein kinase. Conversely, phosphorylation of casein and histones by protein kinase activity present in P-10,000 was not modified by progesterone. It is then suggested that progesterone regulates p48 phosphorylation by affecting the protein substrate in the membrane, rather than by inhibiting the protein kinase enzyme itself. The data demonstrate a direct effect (not mediated by change of protein synthesis) of steroids on p48 phosphorylation in the plasma membrane, and they suggest that this protein could be implicated in the initial action of progesterone on oocyte maturation.
...
PMID:Progesterone-inhibited phosphorylation of an unique Mr 48,000 protein in the plasma membrane of Xenopus laevis oocytes. 298 68

Calmodulin tryptic fragments 78-148, 107-148, and 1-77 coupled to Sepharose 4B were used to test the ability of different calmodulin-regulated enzymes to recognize different domains of calmodulin. Fragment 107-148, which contains a single Ca2+-binding domain, does not interact with any of the calmodulin binding proteins. Fragments 1-77 and 78-148, each of which contains two Ca2+-binding domains, have preserved their ability to interact with several calmodulin-dependent enzymes. Most of the calmodulin-regulated enzymes in brain extracts, such as cAMP phosphodiesterase, cAMP-dependent protein kinase, and the calmodulin-stimulated protein phosphatase (calcineurin) interact with fragment 78-148 in a Ca2+-dependent fashion. An ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-sensitive, calmodulin-independent, p-nitrophenyl phosphatase does not bind to the affinity column and is resolved from calcineurin at this step. Although calmodulin-stimulated protein kinase(s) can interact with fragment 78-148, their interaction is prevented by increased ionic strength even in the presence of Ca2+. Fragment 1-77 exhibits a higher degree of selectivity than fragment 78-148. Only cAMP-dependent protein kinase and cAMP phosphodiesterase bind to fragment 1-77. These results confirm the multiple modes of interaction of calmodulin with its target proteins and provide the basis for a selective purification of calmodulin-regulated enzymes by affinity chromatography on specific calmodulin fragments coupled to Sepharose.
...
PMID:Selective affinity chromatography with calmodulin fragments coupled to sepharose. 298 37

cAMP-dependent protein kinase, derived from either calf lens or bovine heart, promotes the phosphorylation of three lens plasma membrane proteins of molecular mass 28 kDa, 26 kDa and 18 kDa. Correlation of the maximal level of phosphorylation of these components with the Coomassie blue staining intensity of fractionated lens membranes suggests that the phosphorylation of the 28 kDa and 18 kDa components may be approximately stoichiometric. The protein kinase substrates could be dephosphorylated by a cardiac sarcoplasmic-reticulum-bound protein phosphatase activity. The 26 k Da component comigrated with MP26, the major lens membrane component that has been localized to the lens fiber cell junction. Treatment of phosphorylated lens membranes with chymotrypsin did not suggest that any of the three major phosphorylated components was derived from the partial proteolysis of a larger phosphoprotein. After electrophoretic separation of phosphorylated proteins, treatment with N-chlorosuccinimide confirmed that there was little similarity in the structure of the three phosphoproteins. Chymotrypsin did, however, reveal a cryptic phosphorylation site in a 22 kDa fragment that appeared to be derived from MP26. Treatment of phosphorylated membranes with reducing agents resulted in the disappearance of the 28 kDa phosphorylated component and the appearance of a new phosphorylated component of 18 kDa; neither MP26 nor the original 18 kDa component was affected by such treatment. It is not clear whether the original 18 kDa phosphoprotein, present in unreduced samples, is the same as that generated with reducing agents from the 28 kDa phosphorylated lens membrane component.
...
PMID:Characterization of the bovine lens plasma membrane substrates for cAMP-dependent protein kinase. 299 Sep 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---