Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amino acid sequences of mammalian protein phosphatase 1 and 2A were compared pairwise with every sequence in the National Biomedical Research Foundation protein sequence database using an exhaustive searching programme [Coulson et al., Comp. J. 30 (1987) 420-424]. The N-terminal half of the protein encoded by an open reading frame, orf 221, in bacteriophage lambda (nt 43,224-43,886 in the map of Daniels et al. [in Hendrix et al. (Eds.), Lambda II. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1983, pp. 519-676] shows 35% identity to either protein phosphatase 1 or 2A in this region. If conservative replacements are included the overall homology rises to 49%. A gene in phi 80 also shows 35% identity with the mammalian protein phosphatases. The results indicate that orf 221 of phage lambda and the homologous phi 80 gene may encode protein phosphatases. The possible roles of protein phosphorylation in the propagation of bacteriophage are discussed.
Gene 1988 Sep 15
PMID:Segments of bacteriophage lambda (orf 221) and phi 80 are homologous to genes coding for mammalian protein phosphatases. 285 44

Coated vesicles are involved in the intracellular transport of membrane proteins between a variety of membrane compartments in which they must be able to undergo repeated membrane fusion and fission. We previously described the presence of cyclic nucleotide- and Ca2+-independent protein kinase activity in bovine brain coated vesicles which specifically phosphorylated a unique Mr = 50,000 coated vesicle integral protein (pp50) on a threonine residue. We describe now the presence in bovine brain coated vesicles of the antagonistic enzymatic activity which dephosphorylates pp50. This phosphoprotein phosphatase occurs under two interconvertible active and inactive forms. The activation process needs the simultaneous presence of Mg2+ and ATP or ADP. Unchelated ATP, but not unchelated ADP, inactivates the pp50 phosphatase. The latter is associated with the vesicular core. MgADP activation of the pp50 phosphatase implicates a different mechanism which does not need a phosphorylated intermediate. Thus, the pp50 phosphatase might belong to a new phosphatase type distinct from the four other classes of well known protein phosphatases.
J Biol Chem 1986 Sep 25
PMID:Presence of a MgATP/ADP-dependent pp50 phosphatase in bovine brain coated vesicles. 287 74

The effect of atrial natriuretic peptide (ANP) on angiotensin II- and histamine-induced contraction and muscle light chain phosphorylation was examined in strips of rabbit aorta smooth muscle. Preincubation of strips with 10(-7) M ANP prior to addition of either agonist inhibits both the increase in extent of myosin light chain phosphorylation and the contractile response to either 5 x 10(-8) M angiotensin II or 10(-5) M histamine without inhibiting the agonist-induced increase in the intracellular free Ca2+ concentration. Furthermore, in muscle strips precontracted with either angiotensin II or histamine, addition of ANP leads to a prompt relaxation and a prompt decrease in the extent of myosin light chain phosphorylation. These data argue that ANP uncouples the initial agonist-induced Ca2+ transient from the increase in extent of myosin light chain phosphorylation either by inhibiting the Ca2+-dependent activation of myosin light chain kinase or stimulating the activity of a phosphoprotein phosphatase capable of bringing about the rapid dephosphorylation of phosphorylated myosin light chains.
J Biol Chem 1988 Sep 15
PMID:Atrial natriuretic peptide inhibits the agonist-induced increase in extent of myosin light chain phosphorylation in aortic smooth muscle. 297 Oct 37

The deinhibitor protein, responsible for the decreased sensitivity of the ATP,Mg-dependent protein phosphatase to inhibitor-1 and the modulator protein, is inactivated by cyclic AMP-dependent protein kinase and reactivated by dephosphorylation. The specificity of this reaction was tested with the ATP,Mg-dependent phosphatase in its activated or spontaneously active form, four different forms of polycation-stimulated phosphatases (PCSH, PCSM, PCSL and PCSC) and calcineurin. Only the high -Mr polycation-stimulated protein phosphatase (PCSH), but not its catalytic subunit (PCSC), shows a high degree of specificity for the deinhibitor protein. Deinhibitor phosphatase activity of PCSH is affected neither by polycations nor by Mn ions.
FEBS Lett 1985 Sep 02
PMID:Dephosphorylation of the deinhibitor protein by the PCSH protein phosphatase. 299 24

The effects of microsomal HMG-CoA reductase kinase, cytosolic phosphoprotein phosphatase and cytosolic, thiol-dependent cholesterol 7 alpha-hydroxylase stimulatory protein on purified cholesterol 7 alpha-hydroxylase and HMG-CoA reductase from rat liver were compared. Neither HMG-CoA reductase kinase nor phosphoprotein phosphatase had any significant effect on cholesterol 7 alpha-hydroxylase activity. They inhibited and stimulated, respectively, the activity of HMG-CoA reductase. The purified cytosolic protein which stimulated cholesterol 7 alpha-hydroxylase threefold in the presence of glutathione had no effect on HMG-CoA reductase. The results show that there are separate intracellular systems for modulation of cholesterol 7 alpha-hydroxylase and HMG-CoA reductase.
FEBS Lett 1985 Sep 09
PMID:Differences in mechanisms of modulation between rat liver cholesterol 7 alpha-hydroxylase and HMG-CoA reductase. 299 28

A mechanism of activation of the ATP.Mg-dependent protein phosphatase (FC.M) has been proposed (Jurgensen, S., Shacter, E., Huang, C. Y., Chock, P. B., Yang, S.-D., Vandenheede, J. R., and Merlevede, W. (1984) J. Biol. Chem. 259, 5864-5870) in which a transient phosphorylation by the kinase FA of the modulator subunit (M) is the driving force for the transition of the inactive catalytic subunit (FC) into its active conformation. Incubation of FC.M with kinase FA and Mg2+ and adenosine 5'-(gamma-thio)triphosphate results in thiophosphorylation of M and also a conformational change in the phosphatase catalytic subunit; however, the enzyme remains inactive. Proteolysis of this inactive, thiophosphorylated complex causes proteolytic destruction of the modulator subunit and yields an active phosphorylase phosphatase species. Similar treatment of the native inactive enzyme does not yield active phosphatase. Evidence is presented, suggesting that a molecule of modulator is bound at an "inhibitory site" on the native enzyme. This modulator does not prevent the conformational change in the phosphatase catalytic subunit upon incubation with kinase FA and ATP.Mg but does partially inhibit the expression of the phosphorylase phosphatase activity.
J Biol Chem 1985 Sep 05
PMID:Kinase FA-mediated regulation of rabbit skeletal muscle protein phosphatase. Reversible phosphorylation of the modulator subunit. 299 77

Canine cardiac sarcoplasmic reticulum is phosphorylated by an endogenous calcium-calmodulin-dependent protein kinase on a 22,000 proteolipid, called phospholamban. Phosphorylation by the calcium-calmodulin-dependent protein kinase is associated with stimulation of the initial rates of calcium transport (Davis, B. A., Schwartz, A., Samaha, F. J., and Kranias, E. G. (1983) J. Biol. Chem. 258, 13587-13591). The present study shows that protein phosphatase activity, associated with canine cardiac sarcoplasmic reticulum vesicles, can catalyze dephosphorylation of the calcium-calmodulin-dependent sites on phospholamban. The activity was maximally stimulated by manganese; fluoride was inhibitory, but its effect was reversible. Dephosphorylation of phospholamban, which was prephosphorylated by calcium-calmodulin-dependent protein kinase, resulted in a reduction of the stimulation on calcium transport rates, particularly at submaximal calcium concentrations. The decrease in calcium transport was associated with a statistically significant decrease in the apparent affinity (EC50) for calcium. Rephosphorylation of phospholamban by the endogenous calcium-calmodulin-dependent protein kinase caused full recovery of the stimulation on calcium transport rates and reversal of the effects mediated by the protein phosphatase. Thus, the calcium pump in cardiac sarcoplasmic reticulum appears to be under reversible regulation mediated by endogenous calcium-calmodulin-dependent protein kinase and protein phosphatase. Such regulation may represent an important control mechanism for the myocardium.
J Biol Chem 1985 Sep 15
PMID:Regulation of calcium transport by protein phosphatase activity associated with cardiac sarcoplasmic reticulum. 299 98

Calmodulin-dependent protein phosphatase isolated from bovine brain consists of a catalytic subunit A (Mr = 60,000) and a regulatory subunit B (Mr = 19,000) present in equal molar ratios. The two subunits were dissociated by gel filtration in 6 M urea and reconstituted to investigate the role of calmodulin and subunit B in regulating the phosphatase activity of subunit A. The activity of subunit A was stimulated 2-fold by calmodulin, 13-fold by subunit B, and 21-fold by both, indicating that the effects of both were synergistic. Maximum stimulation by calmodulin was observed at a calmodulin to subunit A molar ratio of 2:1 in the presence or absence of subunit B, whereas that by subunit B was observed at a B to A molar ratio of 3:1 in the presence or absence of calmodulin. Calmodulin and subunit B increased the Vmax of subunit A 2- and 5-fold, respectively, but had little effect on the Km for casein. The specific activity of the phosphatase reconstituted from subunits A and B reached 86% that of the native enzyme, whereas that of the holoenzyme reached 90%. Subunit B, even though similar to calmodulin in many respects, did not stimulate the activity of native phosphatase, suggesting that it cannot substitute for calmodulin. Limited trypsinization of subunit A increased its catalytic activity to the level observed with calmodulin; and this activity was further stimulated by subunit B but not by calmodulin. These results indicate that subunit A of phosphatase contains one catalytic domain and two distinct regulatory domains, one for calmodulin, and another for subunit B, that these two proteins do not substitute for one another and that they stimulate subunit A synergistically.
J Biol Chem 1985 Sep 15
PMID:Bovine brain calmodulin-dependent protein phosphatase. Regulation of subunit A activity by calmodulin and subunit B. 299

Calcineurin, a calmodulin-stimulated protein phosphatase, was a substrate for purified bovine brain protein carboxyl O-methyltransferase (protein O-methyltransferase; EC 2.1.1.24) and incorporated up to 2 mol of CH3 per mol of calcineurin. Carboxyl methylation was dependent on the concentrations of S-adenosyl-L-[methyl-3H]methionine and was prevented by addition of the carboxyl methylation inhibitor S-adenosylhomocysteine. The stoichiometry of methyl group incorporation was related to the ratio of methyltransferase/calcineurin. The rate of spontaneous hydrolysis of carboxyl methylester groups on calcineurin increased rapidly above pH 6.5 with those on native carboxyl-methylated calcineurin substantially more labile than for trichloracetic acid-precipitated calcineurin. Polyacrylamide gel electrophoresis in the presence of NaDodSO4 (pH 2.4) confirmed that the A subunit of calcineurin (Mr = 61,000) was the primary site of carboxyl methylation with little, if any, modification of the B subunit (Mr = 18,000). When carboxyl-methylated calcineurin (approximately 1-2 mol of CH3 per mol of protein) was assayed for p-nitrophenyl phosphatase activity at pH 6.5, a marked inhibition of calmodulin-stimulated activity was observed while there was little effect on Mn2+-stimulated phosphatase activity. Thus, calcineurin appears to be an excellent substrate for protein carboxyl O-methylation and this modification, which impairs calmodulin stimulation of phosphatase activity, may be of functional significance.
Proc Natl Acad Sci U S A 1985 Sep
PMID:Stoichiometric methylation of calcineurin by protein carboxyl O-methyltransferase and its effects on calmodulin-stimulated phosphatase activity. 299 37

Cytoplasmic non-polysomal mRNP from cryptobiotic gastrulae of the brine shrimp Artemia salina do not contain endogeneous protein phosphatase activity. However, both non-polysomal mRNP and purified mRNP proteins, phosphorylated by mRNP associated protein kinase, can be dephosphorylated by protein phosphatases purified from A. salina cytosol and rabbit skeletal muscle. The 38 kDa and 23.5 kDa poly(A) binding proteins (P38 and P23.5) and a 65 kDa protein are the major substrates of each protein phosphatase used. The reversible phosphorylation-dephosphorylation of mRNP may be involved in the regulation of mRNP metabolism, by altering the poly(A) binding capacities of the mRNP proteins.
Biochem Biophys Res Commun 1985 Sep 30
PMID:Dephosphorylation of cytoplasmic non-polysomal messenger ribonucleoproteins from cryptobiotic gastrulae of Artemia salina. 299 44


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