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 protein (Escherichia coli CheY) that controls the direction of flagellar rotation during bacterial chemotaxis has been shown to be phosphorylated on the aspartate 57 residue. The residue phosphorylated is present within a conserved sequence in every member of a family of bacterial regulatory proteins. The phosphorylation is transient, with a much shorter half-life than that expected of a simple acyl phosphate intermediate, indicating that the sequence and conformation of the protein is designed to achieve a rapid hydrolysis. The CheY-phosphate linkage can be reductively cleaved by sodium borohydride. High-performance tandem mass-spectrometric analysis of proteolytic peptides derived from [3H]borohydride-reduced phosphorylated CheY protein was used to identify the position of phosphorylation. Mutants with altered aspartate 57 exhibited no chemotaxis. When aspartate 13, another conserved residue, was changed, greatly reduced chemotaxis was observed, suggesting an important role for aspartate 13. The rate-determining step of chemotactic signaling is governed by the kinetics of formation and hydrolysis of the CheY protein phosphoaspartate bond. The CheY protein apparently functions as a protein phosphatase that possesses a transient covalent intermediate. Transient phosphorylation of an aspartate residue is an effective mechanism for producing a biochemical signal with a short concentration-independent half-life. The duration of the signal can be controlled by small structural elements within the phosphorylated protein.
J Biol Chem 1989 Dec 25
PMID:Identification of the site of phosphorylation of the chemotaxis response regulator protein, CheY. 268 46

Human central and peripheral nerve cell tumors were examined in detail using antibodies to calcineurin, glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE). Forty-eight formalin-fixed and paraffin-embedded specimens of human neuronal tumors, including 27 medulloblastomas, were examined. Calcineurin-positive cells were found in all peripheral nerve cell tumors and the two gangliogliomas, whereas 20 of the 27 medulloblastomas and one of the two cerebral neuroblastomas did not contain calcineurin-positive cells. Differentiation of cells along the neuronal lines was positively correlated with calcineurin immunoreactivity. NSE-positive cells were found in all of the tumors with the exception of the one cerebral neuroblastoma. NSE immunoreactivity was not invariably consistent with calcineurin immunoreactivity and non-neuronal cells were often positive. Calcineurin-positive cells were all devoid of GFAP, but NSE-positive cells expressed GFAP in some tumors. GFAP-immunoreactive cells were found only in central nerve cell tumors, and not in peripheral tumors. In addition, GFAP-positive cells in some tumors such as retinoblastoma and medulloblastoma morphologically revealed not only neoplastic but also reactive astrocytic features.
Cancer 1987 Dec 15
PMID:An immunocytochemical demonstration of calcineurin in human nerve cell tumors. A comparison with neuron-specific enolase and glial fibrillary acidic protein. 282 21

A cDNA clone encoding a second type-2A protein phosphatase catalytic subunit (2A beta) was isolated from a rabbit skeletal muscle cDNA library constructed in lambda gt10. The deduced protein sequence (309 residues, 35.59 kDa) was 97% identical to that of phosphatase 2A alpha (309 residues, 35.58 kDa). At the nucleotide level, the two clones showed only 82% identity in the coding region. The results indicate the presence of at least two isoforms of protein phosphatase 2A in skeletal muscle.
FEBS Lett 1987 Dec 21
PMID:A second catalytic subunit of type-2A protein phosphatase from rabbit skeletal muscle. 282 53

The effects of various polycation-stimulated (PCS) phosphatases and of the active catalytic subunit of the ATPMg-dependent (AMDc) protein phosphatase on the activity of casein kinase 2 (CK-2) were investigated by using the synthetic peptide substrate Ser-Glu-Glu-Glu-Glu-Glu, whose phosphorylated derivative is entirely insensitive to these protein phosphatases. Previous dephosphorylation of native CK-2 enhances its specific activity 2-3-fold. Such an effect, accounted for by an increase in Vmax, is more readily promoted by the PCS phosphatases than by the AMDc phosphatase. The phosphate incorporated by autophosphorylation could not be removed by the protein phosphatases, suggesting the involvement of phosphorylation site(s) other than the one(s) affected by intramolecular autophosphorylation. The activation of CK-2 by the phosphatase pretreatment is neutralized during the kinase assay; the mechanism of this phenomenon, which is highly dependent on the kinase concentration, is discussed.
Biochem J 1987 Dec 15
PMID:Regulation of casein kinase 2 by phosphorylation/dephosphorylation. 282 41

A cDNA clone corresponding to a portion of the catalytic subunit of calmodulin (CaM)-dependent phosphoprotein phosphatase (calcineurin) was isolated from a murine brain library by expression vector immunoscreening. A beta-galactosidase fusion protein that reacted on Western blots with anti-calcineurin antibodies and biotinylated CaM was purified in preparative amounts using CaM-Sepharose affinity chromatography. Partial digestion of the hybrid protein with Staphylococcus aureus V-8 protease produced several immunoreactive peptides that appeared identical to fragments generated from authentic brain calcineurin. The 1111-base-pair (bp) EcoRI insert contained an open reading frame encoding a protein of 35 kDa followed by a 190-bp 3' noncoding region; seven peptides obtained by partial amino acid sequencing of the bovine brain enzyme were found in the deduced sequence. A domain approximately 12 kDa from the carboxyl terminus was deduced to be the CaM-binding site based on consensus structural features and a sequence of seven amino acids highly related to smooth muscle myosin light-chain kinase. Two regions with identity to protein phosphatases 1 and 2A were found in the amino half of the cloned sequence; however, the intervening sequence contained apparent insertions, suggesting splicing of subdomains. Thus, the structure of calcineurin is chimeric, consisting of conserved catalytic elements and a regulatory CaM-binding domain.
Proc Natl Acad Sci U S A 1988 Dec
PMID:Characterization of a cDNA clone encoding the calmodulin-binding domain of mouse brain calcineurin. 284 50

Calmodulin was trace labeled by acetylation with [3H]acetic anhydride in the presence and absence of a 30% molar excess of the phosphatase calcineurin; phenylalanine was included in the reaction mixtures as an internal standard. The level of 3H acetylation of each of the 7 lysines was determined and corrected for differences arising from reaction conditions using the labeling of the internal standard, following procedures that are closely similar to those used in a previous study of the interaction of calmodulin with myosin light chain kinase (Jackson, A. E., Carraway, K. L., III, Puett, D., and Brew, K. (1986) J. Biol. Chem. 261, 12226-12232). The interaction with calcineurin was found to produce a 10-fold reduction in the acetylation of lysine 75, with lesser but significant effects on lysines 21 and 148. A small but reproducible perturbation of lysine 77 was also observed. The results are similar to those that are produced by the interaction with myosin light chain kinase. However, when they are compared with two recent reports between which there are major discrepancies (Manalan, A. S., and Klee, C. B. (1987) Biochemistry 26, 1382-1390; Winkler, M. A., Fried, V. A., Merat, D. L., and Cheung, W. Y. (1987) J. Biol. Chem. 262, 15466-15471), our results are in good agreement with those obtained in the former study. From the location of the perturbed groups in the three-dimensional structure of calmodulin, it appears that the interaction site on calmodulin for calcineurin, as well as for myosin light chain kinase, is very extended and may include hydrophobic pockets at homologous sites near the carboxyl-terminal ends of the two halves of the molecule.
J Biol Chem 1988 Dec 25
PMID:Effects of interaction with calcineurin on the reactivities of calmodulin lysines. 284 32

A cDNA clone coding for an isotype of the catalytic subunit of rat phosphoprotein phosphatase 2A was isolated. The deduced amino acid sequence of the clone was different at 8 positions from that of rat phosphatase 2A alpha determined in a previous study. The deduced amino acid sequence of the clone was, however, identical to that of human phosphatase 2A beta and differed only at one position from that of rabbit 2A beta. Thus, the isolated cDNA was identified as a clone coding for rat phosphatase 2A beta. Using a 2A beta specific probe, two kinds of transcripts were detected in rat liver: a major 2.0 kb mRNA transcript and a minor 1.4 kb mRNA transcript. These transcripts were both greatly increased in rat liver tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) regardless of the carcinoma or hyperplastic nodule.
Biochem Biophys Res Commun 1988 Dec 15
PMID:Molecular cloning of rat phosphoprotein phosphatase 2A beta cDNA and increased expressions of phosphatase 2A alpha and 2A beta in rat liver tumors. 284 37

A cDNA encoding a novel protein phosphatase catalytic subunit (protein phosphatase X) has been isolated from a rabbit liver library. It codes for a protein having 45% and 65% amino acid sequence identity, respectively, to the catalytic subunits of protein phosphatase 1 and protein phosphatase 2A from skeletal muscle. The enzyme is neither the hepatic form of protein phosphatase 1 or 2A, nor is it protein phosphatase 2B or 2C. The possible identity of protein phosphatase X is discussed.
FEBS Lett 1988 Dec 19
PMID:Identification of a novel protein phosphatase catalytic subunit by cDNA cloning. 284 55

Okadaic acid (OA;C44H66O13) is a polyether derivative of a C38 fatty acid first isolated from marine sponges of the genus Halichondria . It is thought to be synthesized by marine diflagellates and to accumulate in the other marine organisms such as sponges and shellfishes which feed on them. Physiologically, OA has been known to have a marked contractile effect on smooth muscles and heart muscle. Recent results strongly suggest that these contractile effects are due to the inhibitory action of OA on the intracellular protein phosphatase activity.
J Muscle Res Cell Motil 1988 Dec
PMID:Okadaic acid. Protein phosphatase inhibition and muscle contractile effects. 285 Feb 99

Prior phosphorylation of its substrate has been shown to be important for substrate recognition by the protein kinase glycogen synthase kinase-3 (GSK-3). Phosphorylation of glycogen synthase by GSK-3 is known to be enhanced by the previous action of casein kinase II and the sequence -SXXXS(P)- was proposed as the minimal recognition determinant for GSK-3. The glycogen binding subunit of type 1 phosphoprotein phosphatase has been shown to be phosphorylated by cyclic AMP-dependent protein kinase at serine-13 in the sequence KPGFS(5)PQPS(9)RRGS(13)ESSEEVYV (F.B. Caudwell, A. Hiraga, and P. Cohen (1986) FEBS Lett. 194, 85-89). Inspection of the sequence revealed potential GSK-3 sites at residues 5 and 9. Using a synthetic peptide with the above sequence, we found that phosphorylation of serine-13 by cyclic AMP-dependent protein kinase permitted the recognition of serine-9 and serine-5 by GSK-3. The work provides another example of a substrate for GSK-3 and demonstrates that the action of GSK-3 is linked to the presence of phosphate in the substrate and not the action of any particular protein kinase. In the course of the analyses, a novel feature of trypsin cleavage of phosphopeptides was noted. In the sequence -SRRGS(P)- trypsin acted uniquely after the first arginine whereas in the sequence -S(P)RRGS(P)- it cleaved randomly at either arginine residue. The fact that GSK-3 could phosphorylate a peptide derived from a phosphatase subunit also raises the possibility that GSK-3 might be involved in controlling glycogen-associated type 1 phosphatase and, more generally, in mediating cyclic AMP control of protein phosphorylation in cells.
Arch Biochem Biophys 1988 Dec
PMID:Phosphoserine as a recognition determinant for glycogen synthase kinase-3: phosphorylation of a synthetic peptide based on the G-component of protein phosphatase-1. 285 Jul 71


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