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

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of cyclic AMP-dependent protein kinase (cAMP-PK) or Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylation on the binding of bovine tau to tubulin and calpain-mediated degradation of tau were studied. Both cAMP-PK and CaMKII readily phosphorylated tau and slowed the migration of tau on sodium dodecyl sulfate-containing polyacrylamide gels. However, cAMP-PK phosphorylated tau to a significantly greater extent than CaMKII (1.5 and 0.9 mol of 32P/mol of tau, respectively), and phosphorylation of tau by cAMP-PK resulted in a greater shift to a more acidic, less heterogeneous pattern on two-dimensional nonequilibrium pH gradient gels compared with CaMKII phosphorylation. Two-dimensional phosphopeptide maps indicate that cAMP-PK phosphorylates a site or sites on tau that are phosphorylated by CaMKII, as well as a unique site or sites that are not phosphorylated by CaMKII. Phosphorylation of tau by cAMP-PK significantly decreased tubulin binding and, as previously reported, also inhibited the calpain-induced degradation of tau. CaMKII phosphorylation of tau did not alter either of these parameters. These results suggest that the phosphorylation of site(s) on the tau molecule uniquely accessible to cAMP-PK contributed to the decreased tau-tubulin binding and increased resistance to calpain hydrolysis.
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PMID:Differential phosphorylation of tau by cyclic AMP-dependent protein kinase and Ca2+/calmodulin-dependent protein kinase II: metabolic and functional consequences. 133 23

Using a calpain/protein kinase C (PKC) complex, we were able to reproduce, in vitro, the induction of PKC down-regulation by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) which had been previously observed in cells. We show that TPA initiates this phenomenon by promoting a calpain-dependent conversion of PKC to the Ca2+ phospholipid-independent protein kinase M (PKM), at physiological calcium concentrations. This effect of TPA was dependent upon the presence of phosphatidylserine and was observed only when PKC was the substrate for the protease, inactivation of calpain by autolysis not being modified by the presence of TPA. Moreover, PKM generated from the calpain-PKC complex was resistant to calpain, even after addition of TPA. These results suggest that TPA induces a conformational change in PKC, increasing the affinity of the kinase for calpain and consequently permitting its proteolysis for the basal level of calcium in cells.
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PMID:Induction of protein kinase C down-regulation by the phorbol ester TPA in a calpain/protein kinase C complex. 139 15

Rat skeletal muscle calpastatin form is markedly modified in its inhibitory properties by means of a reverse reaction which involves both phosphorylation and dephosphorylation. Dephospho-calpastatin shows greater inhibitory efficiency versus mu-calpain, whereas phospho-calpastatin shows maximal inhibition versus m-calpain. Both forms are present in fresh rat muscle. Phosphorylation has been reproduced "in vitro" using a homologous Ca2+ independent protein kinase and found to result in the incorporation of approximately one mole of 32P per mole of protein. Dephosphorylation was induced by treatment with alkaline phosphatase and 32P release shown found to correlate with modifications of the inhibitory properties. This reversible covalent modification of calpastatin is considered an important advancement in the understanding of how different calpain isoforms can be more efficiently controlled by a single inhibitor isozyme form.
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PMID:Modulation of inhibitory efficiency of rat skeletal muscle calpastatin by phosphorylation. 153 Jun 32

In the first report in this series we described the relationships and evolution of 152 individual proteins of the EF-hand subfamilies. Here we add 66 additional proteins and define eight (CDC, TPNV, CLNB, LPS, DGK, 1F8, VIS, TCBP) new subfamilies and seven (CAL, SQUD, CDPK, EFH5, TPP, LAV, CRGP) new unique proteins, which we assume represent new subfamilies. The main focus of this study is the classification of individual EF-hand domains. Five subfamilies--calmodulin, troponin C, essential light chain, regulatory light chain, CDC31/caltractin--and three uniques--call, squidulin, and calcium-dependent protein kinase--are congruent in that all evolved from a common four-domain precursor. In contrast calpain and sarcoplasmic calcium-binding protein (SARC) each evolved from its own one-domain precursor. The remaining 19 subfamilies and uniques appear to have evolved by translocation and splicing of genes encoding the EF-hand domains that were precursors to the congruent eight and to calpain and to SARC. The rates of evolution of the EF-hand domains are slower following formation of the subfamilies and establishment of their functions. Subfamilies are not readily classified by patterns of calcium coordination, interdomain linker stability, and glycine and proline distribution. There are many homoplasies indicating that similar variants of the EF-hand evolved by independent pathways.
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PMID:Evolution of EF-hand calcium-modulated proteins. II. Domains of several subfamilies have diverse evolutionary histories. 160 95

The response of a reaction network composed of protein kinase A, calpain, and protein phosphatase to transient cAMP and Ca2+ signals was studied. An essential feature of signal convergence is that the regulatory subunit of cAMP-dissociated protein kinase A undergoes limited proteolysis by the Ca(2+)-activated proteinase calpain. A dynamic model of this system based on kinetic differential equations was built and simulated by computer. The system shows analogies to typical features of associative learning such as acquisition, contiguity detection, extinction, and memory decay, suggesting that these biochemical reactions may be part of the molecular mechanism of learning in Drosophila.
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PMID:Signal convergence on protein kinase A as a molecular correlate of learning. 164 32

Limited proteolysis of tyrosine hydroxylase (TH) by calpain, Ca(2+)-activated neutral protease, was studied. Cleavage of TH with calpain in vitro produced molecules having Mrs of approximately 57,000 and 56,000 in SDS-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence, Ser-Pro-Arg-Phe-Val, of the 56-kDa species indicated that calpain cleaved off the N-terminal region (residues 1-30) encoded by the first exon including Ser-8 and Ser-19, the phosphorylation sites by proline-directed protein kinase (PDPK) and by Ca2+/calmodulin-dependent protein kinase II (kinase II), respectively, from the native TH. The removal of the N-terminal region from the native molecule induced a slight but significant activation of TH at pH 7.0. The native TH behaved as the tetramer with an Mr of 240,000. In contrast, calpain-cleaved TH showed the monomeric Mr by gel permeation chromatography and increased Ki for catecholamine which inhibits the native TH in competition to the coenzyme, DL-6-methyl-5,6,7,8-tetrahydropterin (6MPH4). These results imply that calpain cleavage would effectively release TH from the feedback inhibition by removal of the N-terminal region resulting in disruption of the quaternary structure.
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PMID:Limited proteolysis of tyrosine hydroxylase by Ca(2+)-activated neutral protease (calpain). 168 1

The effects of cAMP-dependent protein kinase (cAMP-PK) phosphorylation on the degradation of the microtubule-associated protein tau by calpain were studied. Purified bovine brain tau that had been phosphorylated by cAMP-PK had a slower migration pattern on sodium dodecyl sulfate-polyacrylamide gels and a more acidic, less heterogeneous pattern on two-dimensional, nonequilibrium pH gradient electrophoresis (NEPHGE) gels compared with untreated tau. Phosphorylation of tau by cAMP-PK significantly inhibited its proteolysis by calpain compared with untreated tau. To our knowledge this is the first demonstration that phosphorylation of tau by a specific kinase results in increased resistance to hydrolysis by calpain. Tau dephosphorylated by alkaline phosphatase migrated more rapidly on sodium dodecyl sulfate-polyacrylamide gels and also showed an altered two-dimensional NEPHGE pattern. Dephosphorylation of tau had no effect on its susceptibility to calpain proteolysis, indicating that regulation of the susceptibility to calpain hydrolysis is due to the phosphorylation of a specific site(s). These results suggest a role for phosphorylation in regulating the degradation of tau. Abnormal phosphorylation could result in a protease-resistant tau population which may contribute to the formation of paired helical filaments in Alzheimer's disease.
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PMID:Phosphorylation by cAMP-dependent protein kinase inhibits the degradation of tau by calpain. 173 Jul 2

Occupancy of surface immunoglobulin (sIg) receptor for antigen expressed on resting B cells initiates increased turnover of membrane-associated phosphatidylinositol (PI), which ultimately leads to the enhanced expression of c-myc mRNA. The mechanism which links these initial membrane biochemical changes to subsequent alterations in c-myc transcription is unclear. The present study examines the possible involvement of PKC and its calpain-generated proteolytic fragment, protein kinase M (PKM), in conveying the membrane-associated signal to the nucleus. Utilizing an in vitro phosphorylation assay, we have shown that a calcium-dependent protease, similar to calpain, is involved in the downregulation of membrane-associated PKC induced by anti-immunoglobulin or phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulation of resting B cells. In addition, we have confirmed previous studies showing that PMA and ionomycin are both required for optimal expression of c-myc mRNA. The enhanced expression of c-myc mRNA is sensitive to inhibitors of PKC, such as H-7 and sangavimycin, providing evidence for a prominent role of PKC and/or PKM in the receptor-mediated up-regulation of c-myc message expression. Finally, a calpain inhibitor interferes with the transmission of the membrane-associated signal which induces the increased expression of c-myc mRNA. Our results are consistent with the hypothesis that the calpain-mediated proteolysis of membrane-associated PKC is involved in the sIg-mediated signal transduction pathway.
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PMID:The proteolysis of membrane-associated protein kinase C as a possible component of the signalling pathway leading to c-myc induction in B lymphocytes. 176 Feb 54

Calpastatin is an endogenous inhibitor protein acting specifically on calpain (EC 3.4.22.17; Ca2(+)-dependent cysteine proteinase). The phosphorylation of calpastatin was investigated in human hematopoietic system cell lines. Microheterogeneity of calpastatin was observed, in which 118- and 116-kDa forms were named calpastatin a and b, respectively. The phosphorylation of both calpastatins was identified in all cell lines examined and occurred mainly at serine residues with trace amounts of phosphothreonine in vivo. The incubation of cells with 12-O-tetradecanoylphorbol-13-acetate increased the incorporation of 32P-orthophosphate into calpastatin a. Two-dimensional maps of 32P-labeled phosphopeptide from both calpastatins were identical except for additional minor spots for calpastatin a. [35S]methionine-labeled calpastatins a and b were localized mainly in the cytosol, and only 6% of cellular calpastatins were detected in the membrane fraction. By contrast, more than 30% of the 32P-labeled calpastatins a and b were distributed in the membrane fraction. Thus, the phosphorylation of calpastatin may be involved in regulating the calpain-calpastatin protein kinase system by its subcellular distribution.
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PMID:Phosphorylation and subcellular distribution of calpastatin in human hematopoietic system cells. 199 45

1. In whole ghosts, ankyrin, protein 4.1, protein band 3 and spectrin are lysed by purified calpain I in the presence of calcium. 2. Limited calpain lysis of purified ankyrin results in several peptides, including a 85 kD peptide bearing the ankyrin interaction site for the protein band 3 internal fragment (43 kD), and a 55 kD peptide carrying the ankyrin-spectrin interaction site. 3. These peptides are differently phosphorylated: the 85 kD by cytosol casein kinase, and the 55 kD by membrane casein kinase. 4. Protein 4.1 lysis mainly produces a 30 kD peptide resistant to proteolysis. 5. The spectrin beta-chain is more sensitive to calpain cleavage than the alpha chain; both chains seem to be cleaved in a similar sequential manner. 6. Limited proteolysis of spectrin dimer does not impede tetramerization in vitro.
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PMID:In vitro digestion of spectrin, protein 4.1 and ankyrin by erythrocyte calcium dependent neutral protease (calpain I). 214 14


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