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 cytoplasmic glucocorticoid receptor of X. laevis liver has a high affinity for [3H]dexamethasone (Kd, 0.3 x 10(-8) M), and its binding specificity for a variety of steroids is similar to that found for mammalian glucocorticoid receptors. The ability of this receptor to bind [3H]-dexamethasone is stable at 0 degrees C but is rapidly lost at 10 and 20 degrees C. Alkaline phosphatase increases, whereas molybdate and tungstate decrease, the rate at which the binding activity is lost. These results are consistent with the loss of binding activity being due to dephosphorylation of the receptor. Binding of [3H]dexamethasone to the receptor does not alter the rate at which the binding activity is lost but does increase the stabilizing effect of molybdate. 100 mM molybdate lowers the apparent affinity of the receptor for [3H]dexamethasone, suggesting that molybdate can interact with the X. laevis glucocorticoid receptor. Addition of UTP, but not ATP, GTP or CTP, reactivates the receptor-binding activity, which indicates that the receptor may be phosphorylated by a UTP-dependent protein kinase.
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PMID:Glucocorticoid receptor of X. laevis: possible effect of phosphorylation on hormone binding. 628 68

ATP-citrate lyase from rat liver and adipose tissue is phosphorylated by either ATP-citrate lyase kinase or catalytic subunit of cyclic AMP-dependent protein kinase to 0.5-0.6 mol/subunit. We previously demonstrated that the site phosphorylated by ATP-citrate lyase kinase (peptide B) is different from that phosphorylated by catalytic subunit of cyclic AMP-dependent protein kinase (peptide A) (Ramakrishna, S., Pucci, D. L., and Benjamin, W.B. (1981) J. Biol. Chem. 256, 10213-10216). ATP-citrate lyase phosphorylation by both protein kinases added simultaneously was increased synergistically. When ATP-citrate lyase was first phosphorylated by catalytic subunit of cyclic AMP-dependent protein kinase, the net phosphorylation of the fragments subsequently phosphorylated by lyase kinase increased about 6-fold. However, when ATP-citrate lyase was first phosphorylated by lyase kinase, there was no effect on the subsequent phosphorylation of the enzyme by cyclic AMP-dependent protein kinase. Alkaline phosphatase-dephosphorylated ATP-citrate lyase was phosphorylated by catalytic subunit of cyclic AMP-dependent protein kinase to 0.9-1.0 mol/subunit. However, dephospho-ATP-citrate lyase was not phosphorylated by lyase kinase. The addition of both protein kinases simultaneously phosphorylated ATP-citrate lyase up to 2 mol/subunit. Phosphorylation of dephospho-ATP-citrate lyase first by catalytic subunit of cyclic AMP-dependent protein kinase and ATP enabled the lyase to be phosphorylated by lyase kinase. Peptide mapping and phosphoamino acid analysis of dephospho-ATP-citrate lyase phosphorylated by catalytic subunit of cyclic AMP-dependent protein kinase and/or lyase kinase conclusively showed that phosphorylation of ATP-citrate lyase by ATP-citrate lyase kinase was completely dependent on peptide A phosphorylation by cyclic AMP-dependent protein kinase. Furthermore, increased phosphorylation when both protein kinases were added simultaneously was due to increased phosphorylation at peptide B.
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PMID:Dependence of ATP-citrate lyase kinase activity on the phosphorylation of ATP-citrate lyase by cyclic AMP-dependent protein kinase. 630 Jan 6

Alkaline phosphatase (ALP) hydrolyzed phosvitin and amino acid phosphates demonstrating nonisotropy at different pH. Orthovanadate, a protein phosphatase inhibitor, more specifically inhibited the serine and tyrosine phosphatase activities of ALP than that of threonine phosphatase at concentrations > 0.1 mM or 0.01 mM, respectively. Calyculin A and okadaic acid at increased concentrations increased ALP amino acid phosphatase activity. Bisphosphonates, such as disodium-1-hydroxy-1-aminopropylidine-1,1-diphosphonate (APD) and ethane-1-hydroxy-1,1-diphosphonate (HEBP), at increased concentrations, inhibited ALP amino acid phosphatase activity. These results suggest that ALP may function as a protein phosphatase. In terms of protein kinase inhibitors, N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide, N-(6-aminoheyxl)-5-chloro-1-naphthalenesulfomide hydrochloride and 4',5,7-trihydroxyisoflavone had little effect on ALP amino acid phosphatase activity. Staurosporine slightly enhanced ALP serine and threonine phosphatase activities at a concentration of 0.1 mM. These results suggest that protein phosphatase activity does not depend on the protein kinase activity of ALP, since duality between the former and the latter is not supported. ALP may function less as a protein kinase than as a protein phosphatase. The coupling mechanism of phosphate dynamics may be regulated indirectly.
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PMID:Amino acid phosphatase activity of alkaline phosphatase. A possible role of protein phosphatase. 785 10

The SDS-polyacrylamide gel electrophoresis (SDS-PAGE) migration pattern of wild-type and mutated human androgen receptors (ARs) expressed in COS-1 cells was analyzed. In the absence of hormone, the wild-type AR migrated as a closely spaced 110-112 kDa doublet. Alkaline phosphatase treatment resulted in a single 110 kDa band showing that the 112 kDa upshift reflects receptors phosphorylation. Deletion of the N-terminal amino acids 46-101 or 100-142 resulted in mutant ARs migrating as single protein bands. Three consensus phosphorylation sites in this region were substituted, and the resulting mutated proteins were analyzed. Two Ser-Pro-directed kinase consensus sites at positions Ser-80 and Ser-93 were both necessary for the AR 112 kDa upshift. Substitution of the putative casein kinase II Ser-118 site had no effect on the AR migration pattern. Surprisingly, deletion of the glutamine repeat, located directly N-terminal of the Ser-Pro sites, resulted also in an AR single form. Lengthening of the glutamine repeat caused an increase in the spacing between the two isotypes of the doublet, showing that the number of glutamine residues determines the extent of the upshift. Hormone treatment induced an extra isotype with an apparent molecular mass of 114 kDa, resulting in a 110-112-114 kDa AR triplet. The hormone-induced upshift was dependent on the Ser-80 consensus phosphorylation site. Mutations in the DNA binding domain caused a different distribution of receptor protein over the three AR isotypes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in the abundance of androgen receptor isotypes: effects of ligand treatment, glutamine-stretch variation, and mutation of putative phosphorylation sites. 794 16

Using a live in vitro slice preparation of adult rat neocortex we have examined the role of phosphorylation and dephosphorylation in the regulation of GABAA and AMPA receptors. Alkaline phosphatase increased binding levels for both receptors while protein kinase A had the opposite effect. For both receptor populations, phosphatase effects were blocked by sodium beta-D-glycerol phosphate and sodium vanadate (phosphatase inhibitors) while kinase actions were blocked by a protein kinase inhibitor. Increases in cell depolarizations by veratridine led to an increase in labelled GABAA receptors, but to decreases in labelled AMPA receptors. Increases in binding were differentially blocked by the two phosphatase inhibitors, sodium beta-D-glycerol phosphate and sodium vanadate while decreases in binding were blocked by protein kinase inhibitor. Agonist stimulation of GABAA and AMPA receptors led to a decrease in receptor binding which could be blocked in both cases by protein kinase inhibitor. These data show that certain cortical excitatory and inhibitory amino acid receptors can be regulated by the action of phosphorylating/dephosphorylating enzymes and further suggest that the regulation induced by cell depolarization and agonist stimulation is based on similar mechanisms.
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PMID:Regulation of GABAA and AMPA receptors by agonist and depolarizing stimulation requires phosphatase or kinase activity. 838 45

We analyzed the endogenous nuclear 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) receptor (VDR) in rat osteosarcoma (ROS 17/2.8) cells and present biochemical evidence that it is a phosphoprotein. When ROS 17/2.8 cells are labeled metabolically with [35S]methionine, treatment with 10(-8) M 1,25(OH)2D3 elicits a decrease in the electrophoretic mobility of immunoprecipitated VDR in denaturing polyacrylamide gels, a property characteristic of phosphorylated proteins. Similar labeling of cells with [32P]orthophosphate results in a rapid (< or = 30 min), 1,25(OH)2D3-dependent incorporation of 32P into a 54-kDa VDR species that comigrates with the slower migrating receptor species extracted from [35S]methionine-labeled ROS 17/2.8 cells that have been exposed to 1,25(OH)2D3. Alkaline phosphatase treatment of immunoprecipitated VDR from 1,25(OH)2D3-treated cells converts the form of the VDR with reduced mobility to the faster migrating species present in 1,25(OH)2D3-deficient cells. Incubation of ROS 17/2.8 cells with the non-hypercalcemic 1,25(OH)2D3 analog, 22-oxacalcitriol (OCT), produces a level of VDR phosphorylation similar to that elicited by 1,25(OH)2D3 treatment. Transient transfection of osteosarcoma cells with a reporter vector containing a vitamin D responsive element derived from the rat osteocalcin gene yields equivalent transcriptional activation in the presence of either 1,25(OH)2D3 or OCT. Further experiments performed at various 1,25(OH)2D3 concentrations to assess the relationship between receptor phosphorylation and transcriptional activity in intact cells showed a positive correlation between these two parameters, indicating that the 1,25(OH)2D3 hormone stimulates VDR phosphorylation and transcriptional activation in parallel. Finally, highly purified casein kinase II (CK-II) phosphorylates the VDR in a 1,25(OH)2D3-independent, in vitro reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The 1,25-dihydroxy-vitamin D3 receptor is phosphorylated in response to 1,25-dihydroxy-vitamin D3 and 22-oxacalcitriol in rat osteoblasts, and by casein kinase II, in vitro. 839 28

Protein kinase recognition sequences and proteinase sites were engineered into the cDNA encoding firefly luciferase from Photinus pyralis in order to establish whether these modified proteins could be developed as bioluminescent indicators of covalent modification of proteins. Two key domains of the luciferase were modified in order to identify regions of the protein in which peptide sequences may be engineered whilst retaining bioluminescent activity; one between amino acids 209 and 227 and the other at the C-terminus, between amino acids 537 and 550. Mutation of amino acids between residues 209 and 227 reduced bioluminescent activity to less than 1% of wild-type recombinant. In contrast engineering peptide sequences at the C-terminus resulted in specific activities ranging from 0.06-120% of the wild-type recombinant. Addition of cyclic AMP dependent protein kinase catalytic subunit, to a variant luciferase incorporating the kinase recognition sequence, LRRASLG, with a serine at amino-acid position 543 resulted in a 30% reduction in activity. Alkaline phosphatase treatment restored activity. The bioluminescent activity of a variant luciferase containing a thrombin recognition sequence, LVPRES, with the cleavage site positioned between amino acid 542 and 543, decreased by 50% when incubated in the presence of thrombin. The results indicate regions within luciferase where peptide sequences may be engineered while retaining bioluminescent activity and have shown changes in bioluminescent activity when these sites are subjected to covalent modification. Changes in secondary structure, charge and length at the C-terminus of luciferase disrupt the microenvironment of the active site, leading to alterations in light emission. This has important implications both in understanding the evolution of beetle bioluminescence and also in development of bioluminescent indicators of the covalent modification of proteins.
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PMID:Engineering the C-terminus of firefly luciferase as an indicator of covalent modification of proteins. 854 53

Antibody Ab262 was raised against a synthetic tau peptide (SKIGSTENLK, amino acids 258-267 of tau, termed Ser262 peptide). The antibody was more reactive with Ser262 peptide and unphosphorylated tau than a related phosphopeptide [SKIGS(P)TENLK, termed PSer262 peptide] and tau phosphorylated by a partially purified kinase, glycogen synthase kinase (GSK) 3 beta. AB262 reacted poorly with a peptide having the sequence DRV-QSKIGSLD (amino acids 348-358). Treatment of PSer262 peptide or GSK 3 beta phosphorylated tau with alkaline phosphatase increased Ab262 immunoreactivity, indicating that Ab262 is a reagent useful for studying tau phosphorylation at the Ser262 residue. The Ab262 immunoreactivity was detected in tau from normal brains and Alzheimer paired helical filament (PHF-tau) and in PHFs. Alkaline phosphatase treatment had no effect on the Ab262 immunoreactivity of normal tau and PHF-tau but altered the tau-1 and PHF-1 immunoreactivities, tau proteins from rat brains at 3 and 8 h postmortem exhibited 5 and 19%, respectively, more Ab262 immunoreactivity than tau from fresh tissues. In comparison, rat tau at 8 h postmortem was 40% more immunoreactive with Tau-1. The results suggest that Ser262 is not a major phosphorylation site in vivo. Moreover, there is little or no difference between PHF-tau and normal tau in the extent of phosphorylation at Ser262.
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PMID:The state of phosphorylation of normal adult brain tau, fetal tau, and tau from Alzheimer paired helical filaments at amino acid residue Ser262. 876 76

The effects of adenosine 3', 5'-cyclic monophosphate (cAMP)-dependent protein phosphorylation on Ca(2+)-sensitivity of Ca(2+)-dependent K(+)-channels in guinea-pig pancreatic acinar cells were studied by patch-clamp single-channel methods. When opening of the channels did not occur in excised inside-out membrane patches exposed to 10(-6) M Ca2+, the addition of 25 U/ml catalytic units of cAMP-dependent protein kinase (PKA) to the bath solution opened the channels, with a conductance of 30 pS (in symmetrical K(+)-rich solution). The addition of a PKA-inhibitor (100 microM) extinguished the PKA-dependent opening of the K(+)-channels. Alkaline phosphatase (5 U/ml) reversed the PKA-dependent opening of the K(+)-channels to control levels (before PKA). These results demonstrate that cAMP-dependent protein phosphorylation initiates the Ca(2+)-sensitivity of the Ca(2+)-dependent K(+)-channels in guinea-pig pancreatic acinar cells.
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PMID:Sensitization of Ca(2+)-dependent K(+)-channels in Guinea-pig pancreatic acinar cells by phosphorylation. 895 60

The hallmark of biological mineralization is the precise regulation of mineral deposition in space and time. The cells which produce mineralized tissues are themselves controlled by developmental programs and hormonal signals which result in regulation of gene expression and modulation of protein function. These signals are transduced into changes in enzyme levels and/or activity. Upon activation, cellular enzymes then act to synthesize the organic matrix and process it extracellularly, utilize metabolic energy to transport ions from the blood to the matrix, and to initiate the mineralization cascade. The first enzyme activity described in mineralizing tissues was alkaline phosphatase and it is still the best characterized enzyme in the mineralization process. Yet, important questions about the role of this protein remain unanswered, and it continues to occupy a central focus in mineralized tissue investigation. Other phosphatases, including protein tyrosine phosphatases are important in regulating tyrosine kinase mediated signals. Investigators have now begun to look closely at several groups of kinases which are also important for proper mineralization. As peptide hormones are important modulators of mineralized tissues, protein kinase A has always been presumed to play a key role in phosphorylating intracellular proteins. There is also considerable interest in protein kinase C, as well as tyrosine kinases in mineralized tissue signal transduction. Another group of kinases important in mineralized tissues are the enzymes which phosphorylate the matrix phosphoproteins. Of these, casein kinase II appears to be involved in intracellular and extracellular protein phosphorylation. Several enzymes present in the premineralized matrix are thought to be significant in triggering mineralization. Alkaline phosphatase may act at this level, but new data also suggests that metalloproteases and gelatinases, by modifying or digesting matrix components, may be important in the initiation of calcification.
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PMID:Enzymes in mineralizing systems: state of the art. 908 56


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