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 subcellular distribution of adenylate cyclase, cyclic-AMP phosphodiesterase, protein kinases and phosphoprotein phosphatase in bloodstream forms of Trypanosoma brucei was determined by isopycnic sucrose-gradient centrifugation of post-large-granule extracts. Cyclic-AMP phosphodiesterase was almost entirely soluble whereas adenylate cyclase was membrane-bound. The latter enzyme appeared to be absent from the plasma-membrane fraction but copurified with acid phosphatase and acid phosphodiesterase indicating a possible association with the flagellar pocket. At least two protein kinase activities could be distinguished as based on their distribution profiles in gradients, their preference for exogenously added acceptor protein and their inhibition and stimulation by suramin and nucleoside, respectively. Suramin-sensitive protein kinase co-purified with the plasma-membrane marker alpha-D-glucosidase and a nucleoside-stimulated protein kinase behaved as a typical cell-sap enzyme. Phosphoprotein phosphatase activity was found to be mainly soluble but a small part seemed to be associated with plasma membranes.
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PMID:Subcellular distribution of adenylate cyclase, cyclic-AMP phosphodiesterase, protein kinases and phosphoprotein phosphatase in Trypanosoma brucei. 629 15

Microtubule-associated protein 2 (MAP 2) is the major substrate for phosphorylation in purified preparations of brain microtubules. In earlier work, we showed that phosphorylation is catalyzed by a type II cAMP-dependent protein kinase tightly associated with MAP 2 itself. In the present study, we have examined the extent of MAP 2 phosphorylation by its associated protein kinase. Using an inorganic phosphate assay, we found that MAP 2 contained from 8 to 13 mol of phosphate/mol of protein as isolated. The catalytic subunit of the MAP 2-associated kinase catalyzed the incorporation of additional phosphate to a final level of 20-22 mol/mol of MAP 2. Potato acid phosphatase was used to remove phosphate from MAP 2. Rephosphorylation of acid phosphatase-treated MAP 2 resulted in maximal incorporation of 13 mol of phosphate/mol of MAP 2. The rates and extent of [32P] phosphate incorporation into as isolated and dephosphorylated MAP 2 were found to be identical, and phosphate was incorporated into identical peptides in the two preparations. These results were interpreted to indicate that MAP 2 contains as many as 13 cAMP-dependent phosphorylation sites, and approximately eight phosphates of as yet undetermined origin.
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PMID:Extensive cAMP-dependent and cAMP-independent phosphorylation of microtubule-associated protein 2. 630 60

Effects of DL-palmitoylcarnitine (PC), an inhibitor of calciumactivated, phospholipid-dependent protein kinase (protein kinase C), on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell differentiation were investigated in human promyelocytic leukemia cells (HL-60). TPA caused HL-60 cell adhesion concomitant with morphological changes, and an increase in acid phosphatase activity. The median effective concentration was 1 nM, which corresponded well to the dissociation constant of [3H]TPA binding to the cell extract. [3H]TPA binding to the cell extract was saturable and reversible. The maximal number of [3H]TPA-binding sites was 1.5 pmol/mg protein and a Hill coefficient was unity, indicating noncooperative interactions. PC, but neither palmitic acid nor DL-carnitine, inhibited the TPA-induced cell adhesion and morphological changes with the median inhibitory concentration of 1 microM, whereas a TPA-induced increase in acid phosphatase activity was not affected by 3 microM PC. Addition of PC 1 or 2 days after the addition of TPA was also effective in inhibiting the cell adhesion. Among various acylcarnitines, PC had the largest effect. [3H]TPA binding to the cell extract was not inhibited by PC at the concentration which was effective in inhibiting the TPA-induced cell adhesion. These results indicate that protein kinase C possibly mediates HL-60 cell differentiation induced by TPA.
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PMID:Inhibition by palmitoylcarnitine of adhesion and morphological changes in HL-60 cells induced by 12-O-tetradecanoylphorbol-13-acetate. 632 91

The PHO85 gene of Saccharomyces cerevisiae encodes a cyclin-dependent kinase involved in both transcriptional regulation and cell cycle progression. Although a great deal is known concerning the structure, function, and regulation of the highly homologous Cdc28 protein kinase, little is known concerning these relationships in regard to Pho85. In this study, we constructed a series of Pho85-Cdc28 chimeras to map the region(s) of the Pho85 molecule that is critical for function of Pho85 in repression of acid phosphatase (PHO5) expression. Using a combination of site-directed and ethyl methanesulfonate-induced mutagenesis, we have identified numerous residues critical for either activation of the Pho85 kinase, interaction of Pho85 with the cyclin-like molecule Pho80, or substrate recognition. Finally, analysis of mutations analogous to those previously identified in either Cdc28 or cdc2 of Schizosaccharomyces pombe suggested that the inhibition of Pho85-Pho80 activity in mechanistically different from that seen in the other cyclin-dependent kinases.
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PMID:Structure-function relationships of the yeast cyclin-dependent kinase Pho85. 756 99

Several authors have shown that angiotensin II stimulates hepatic angiotensinogen synthesis in vivo, ex vivo and in vitro. In previous studies we have demonstrated that this effect of angiotensin II depends mainly on a transient inhibition of adenylyl cyclase and is the consequence of a stabilization of angiotensinogen mRNA. In the present study we describe the isolation of a polysomal 12 kDa protein which, in band shift and cross link assays, shows a specific affinity to the 3' untranslated region (3' UTR) of angiotensinogen mRNA and prevents enzymatic degradation of angiotensinogen mRNA in a cell-free incubation system. [32P]UTP-labelled or unlabelled 3' fragments of angiotensinogen mRNA were synthesized on a transcription vector (pGEM5zf+) into which the corresponding DNA sequence was cloned after restriction from vector pRAG 16. Binding of the 12 kDa protein to the radioactively labelled 3' UTR of angiotensinogen mRNA could be displaced by unlabelled 3' UTR mRNA fragments but not by a renin mRNA of comparable length derived from the coding region. The RNA-binding protein appears to be derived from a higher molecular mass precursor (45 kDa) which is preferentially present under reducing conditions in vitro; the active low molecular mass form is evident in the absence of reducing agents. In a cross link experiment we established that a band shift signal which was obtained in the presence of the 45 kDa protein preparation exclusively depends on RNA binding of the active 12 kDa protein. In addition, a phosphorylation step may be involved in the activation of the 12 kDa protein, since its molecular mass and isoelectric point correlate with proteins which were phosphorylated in response to transient decreases of cAMP (induced by guanfacine or angiotensin II) or in response to a direct inhibition of protein kinase A by the cAMP antagonist Rp-cAMP. The importance of phosphorylation reactions for the stabilization of angiotensinogen mRNA was further assessed in a cell-free incubation system of rat liver parenchymal cells. These studies demonstrated that in the presence of acid phosphatase (1 U/ml) the half-life of angiotensinogen was significantly decreased. In the same incubation system the 12 kDa protein increased the half-life of endogenous as well as of exogenous angiotensinogen mRNA three- to fourfold, while no stabilizing effect was apparent when exogenous angiotensinogen mRNA from which the 3' tail had been deleted was added.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Contribution of a 12 kDa protein to the angiotensin II-induced stabilization of angiotensinogen mRNA: interaction with the 3' untranslated mRNA. 761 10

Phosphofructokinase (PFK) from both white skeletal muscle and liver of trout is controlled by reversible phosphorylation. In vitro phosphorylation of purified muscle PFK with the catalytic subunit of cAMP-dependent protein kinase led to a 25% decrease in the S0.5 F6P and reduced inhibition by Mg.ATP and citrate. Phosphorylation of trout liver PFK lowered the I50 Mg.ATP (by 27%) but in vitro treatment with acid phosphatase reduced S0.5 F6P by 40% and increased I50 Mg.ATP by 50%. Thus, dephosphorylated trout liver PFK appears to be the more active enzyme form. Compared with mammalian PFK, the less rigorous effects of phosphorylation on trout liver PFK and relatively stronger phosphorylation control of skeletal muscle PFK may serve different patterns of carbohydrate metabolism in lower vertebrates, in particular the in situ processing of lactate in post-exercise muscle.
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PMID:Regulation of phosphofructokinase from muscle and liver of rainbow trout by protein phosphorylation. 780 45

The PHO81 gene is thought to encode an inhibitor of the negative regulators (Pho80p and Pho85p) in the phosphatase (PHO) regulon. Transcription of PHO81 is regulated by Pi signals through the same PHO regulatory system. Elimination of the PHO81 promoter or its substitution by the GAL1 promoter revealed that stimulation of the PHO regulatory system requires both increased transcription of PHO81 and a Pi starvation signal. The predicted Pho81p protein contains 1,179 amino acids (aa) and has six repeats of an ankyrin-like sequence in its central region. The minimum amino acid sequence required for Pho81p function was narrowed down to a 141-aa segment (aa 584 to 724), which contains the fifth and sixth repeats of the ankyrin-like motif. The third to sixth repeats of the ankyrin-like motif of Pho81p have significant similarities to that of p16INK4, which inhibits activity of the human cyclin D-CDK4 kinase complex. Deletion analyses revealed that the N- and C-terminal regions of Pho81p behave as negative and positive regulatory domains, respectively, for the minimal 141-aa region. The negative regulatory activity of the N-terminal domain was antagonized by a C-terminal segment of Pho81p supplied in trans. All four known classes of PHO81c mutations that show repressible acid phosphatase activity in high-Pi medium affect the N-terminal half of Pho81p. An in vitro assay showed that a glutathione S-transferase-Pho81p fusion protein inhibits the Pho85p protein kinase. Association of Pho81p with Pho85p or with the Pho80p-Pho85p complex was demonstrated by the two-hybrid system.
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PMID:Functional domains of Pho81p, an inhibitor of Pho85p protein kinase, in the transduction pathway of Pi signals in Saccharomyces cerevisiae. 782 64

The cardiac calcium release channel (CRC) of sarcoplasmic reticulum vesicles was incorporated into planar lipid membranes to evaluate modulation of channel activity by phosphorylation and dephosphorylation. For this purpose a microsyringe application directly to the membrane was used to achieve sequential and multiple treatments of channels with highly purified kinases and phosphatases. Cyclic application of protein kinase A (PKA) or Ca2+/calmodulin-dependent protein kinase II (CalPK) and potato acid phosphatase or protein phosphatase 1 revealed a channel block by Mg2+ (-mM), that is referable to dephosphorylated states of the channel, and that the Mg2+ block could be removed by phosphorylation of the CRC by either PKA or CalPK. By contrast, activation of endogenous CalPK (end CalPK) led to channel closure which could be reversed by dephosphorylation using potato acid phosphatase or protein phosphatase 1. Calmodulin by itself (which activates end CalPK in the presence of MgATP) blocks the channel in the dephosphorylated state, which can be overcome by treatment with CalPK but not PKA. Our findings reveal important insights regarding channel regulation of the ryanodine receptor: 1) the calcium release channel must be phosphorylated to be in the active state at conditions approximating physiological Mg2+ concentrations (-mM); and 2) there are multiple sites of phosphorylation on the calcium release channel with different functional consequences, which may be relevant to the regulation of E-C coupling. Phosphorylation of the CRC may be involved in recruitment of active channels, and/or it may be directly involved in each Ca2+ contraction cycle of the heart. For example, Ca2+ release may require phosphorylation of the CRC by protein kinases at sites which overcome the block by Mg2+. Inactivation may involve CRC block by calmodulin and/or phosphorylation by endogenous CalPK at the junctional face membrane.
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PMID:Phosphorylation modulates the function of the calcium release channel of sarcoplasmic reticulum from cardiac muscle. 783 35

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

Sulfate transport was examined in rat liver lysosomes that were isolated from thyroid hormone-treated, thyroidectomized, and control animals. Sulfate uptake was significantly decreased in lysosomes from animals that had received intraperitoneal T3 (3,5,3'-triiodothyronine) at a dose of 20 micrograms/100 g body weight. The effect of T3 was maximal by 24 h post-injection and resulted in marked decreases in both Vmax (control: 155 +/- 33 pmol/unit of beta-hexosaminidase/30 s versus T3 treated: 24 +/- 7 pmol/unit of beta-hexosaminidase/30 s) and Km (control: 213 +/- 34 microM versus T3 treated: 92 +/- 6 microM). Thyroidectomy was associated with a significant increase in Vmax (control: 250 pmol/unit of beta-hexosaminidase/30 s versus thyroidectomized: 564 pmol/unit of beta-hexosaminidase/30 s), while Km was not significantly affected. The effect of thyroid hormone on lysosomal sulfate transport appeared to be relatively specific. In contrast to its effect on sulfate transport, T3 treatment had no effect on the uptake of either glucose or N-acetylglucosamine by rat liver lysosomes. Lysosomal pH, acidification in response to Mg/ATP, and the specific activities of alpha-L-iduronidase, beta-hexosaminidase, beta-D-glucosidase, and acid phosphatase were unaffected by T3 administration. Incubation of T3 with lysosomes from control animals had little or no effect on sulfate transport. Treatment of isolated lysosomes with either protein kinase A or alkaline phosphatase resulted in modest stimulation of transport. Thus, T3 does not appear to regulate transport by either direct interaction with the lysosomal transporter or protein kinase A-mediated phosphorylation. The exact mechanism for the inhibitory effect of T3 on lysosomal sulfate transport remains to be determined.
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PMID:Regulation of lysosomal sulfate transport by thyroid hormone. 808 19


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