Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two subfractions of bovine thyroid plasma membranes, light membranes (L-membranes) and heavy membranes (H-membranes), were obtained by a discontinuous sucrose gradient centrifugation of plasma membranes. Electron microscopy of the plasma membrane and its subfractions showed that the H-membranes were very similar to the plasma membrane fraction, both contained junctional complexes, long membrane sheets, and vesicles. In contrast, the L-membranes consisted mainly of short membrane sheets and vesicles, and only a few junctional complexes. The H-membranes had greater adenylate cyclase activity which responded to thyroid-stimulating hormone (TSH) while this hormone had very little effect on the enzyme activity in the L-membranes. Despite the marked difference in TSH stimulation of adenylate cyclase activity in the H- and L-membrane fractions, specific binding of 125I-TSH was similar in both fractions. The L-membranes had higher specific activities of 5'-nucleotidase and Mg2+ATPase while (Na+ + K+)-ATPase and alkaline phosphatase activities were similar in the two subfractions. Protein kinase activity of H-membranes was not significantly stimulated by exogenous cyclic adenosine 3':5'-monophosphate (cAMP). Plasma membranes and H-membranes contained a substrate capable of being phosphorylated. Such phosphorylation was slightly increased by addition of soluble protein kinase. The phosphorylation of exogenous histone by protein kinase of plasma membranes and H-membranes was augmented by cAMP. In contrast, L-membranes had very little protein kinase activity even when exogenous histone was added. They were not a very good substrate for cytosolic protein kinase.
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PMID:Preparation and characterization of subfractions of bovine thyroid plasma membranes. 85 12

We examined alkaline phosphatase (ALP) activity in the HL-60 cell induced by retinoic acid (RA) and recombinant human granulocyte colony-stimulating factor (rhG-CSF). rhG-CSF induced a small but significant increase of NBT-reducing ability and ALP activity of the HL-60 cells. Among various inducers of cell differentiation, 1,25(OH)2D3 and dimethylsulfoxide (DMSO) caused the increase of the NBT-reducing ability and the suppression of ALP activity induced by rhG-CSF, while RA enhanced both of them. Protein kinase C inhibitors (H-7 and staurosporine) but not a protein kinase A inhibitor (HA1004) significantly suppressed the ALP activity induced by the simultaneous treatment with RA and rhG-CSF.
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PMID:[The effects of retinoic acid and recombinant human granulocyte colony-stimulating factor on alkaline phosphatase activity of HL-60 cells]. 128 12

Regulation of Cl conductance by protein kinase A may play a role in control of endosomal acidification [Bae, H.-R., & Verkman, A. S. (1990) Nature, 348, 637-639]. To investigate the mechanism of kinase A action, cell-free measurements of Cl transport and membrane protein phosphorylation were carried out in apical endocytic vesicles from rabbit kidney proximal tubule. Cl transport was measured by a stopped-flow quenching assay in endosomes labeled in vivo with the fluorescent Cl indicator 6-methoxy-N-(3-sulfopropyl)quinolinium. Phosphorylation was studied in a purified endosomal preparation by SDS-PAGE and autoradiography of membrane proteins labeled by [gamma-32P]ATP. Endosomes had a permeability (PCl) for conductive Cl transport of 3.1 x 10(-8) cm/s at 23 degrees C which was stilbene inhibitable. PCl was increased by 90 +/- 20% by a 10-min preincubation with the catalytic subunit of kinase A (PKA, 10 units/mL) and MgATP (0.5 mM) with anion selectivity Cl greater than I greater than Br. The increase in PCl was blocked by 100 microM N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8) and was reversed by addition of alkaline phosphatase (AP, 40 units/mL) after incubation with PKA and MgATP; the increase in PCl was not blocked by pretreatment with AP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein kinase A dependent membrane protein phosphorylation and chloride conductance in endosomal vesicles from kidney cortex. 131 27

We have previously demonstrated that growth hormone (GH) promotes an increase in tyrosine kinase activity associated with the GH receptor. To gain insight into the role of GH-dependent tyrosine kinase activity in signaling by GH, we investigated the possibility that GH might stimulate MAP kinase, a serine/threonine/tyrosine kinase thought to be a common element in tyrosine kinase-initiated response cascades. Treatment of 3T3-F442A fibroblasts with 100 ng/ml GH results in a 3-6-fold increase in the ability of cell-free extracts to phosphorylate MAP-2 and myelin basic protein. GH-stimulated kinase activity is unaffected by heparin, H7, or cAMP-dependent protein kinase inhibitor peptide, partially reduced by staurosporin and inhibited by fluoride and calcium ions, indicating that the kinase is not protein kinase C or A, casein kinase, or a calcium/calmodulin-dependent protein kinase. Based on gel permeation chromatography, the molecular mass of the GH-stimulated MAP kinase is approximately kDa. Furthermore, anti-phosphotyrosine antibodies revealed the GH-dependent appearance of two phosphotyrosine-containing proteins in cell-free lysates of GH-treated cells that co-migrate with proteins recognized by anti-MAP kinase antibodies. The GH-dependent increase in MAP kinase activity displays a biphasic time course and is dependent on the concentration of GH applied to the cells. GH-dependent MAP kinase activity, partially purified by Mono-Q chromatography, is inactivated by treatment with alkaline phosphatase. Addition of H7 to the cells prior to the addition of GH has no effect, whereas addition of H8 increases MAP kinase activity in control cells with no effect in GH-treated cells, indicating that protein kinase C is unlikely to be an intermediary in the GH-dependent stimulation of MAP kinase activity. These findings indicate that signaling by GH in 3T3-F443A cells may, at least in part, utilize a kinase cascade similar to those that have been proposed for other membrane receptors with associated tyrosine kinase activity.
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PMID:Stimulation by growth hormone of MAP kinase activity in 3T3-F442A fibroblasts. 131 28

The relationship between the concentration of cAMP-dependent protein kinase (PKA) activity and the induction of alkaline phosphatase (AP) was examined in transfected L cell lines with altered PKA levels. C alpha 12 cells were generated by transfecting mouse L cells with an expression vector coding for the mouse C alpha catalytic subunit of PKA and were shown to contain 2.5-fold more PKA activity than L cells. RAB10 cells were generated by transfection with an expression vector for a mutant regulatory subunit and had 10-fold lower levels of PKA activity than L cells. AP induction by 8-chlorophenylthio-cAMP (CPT-cAMP) was found to be 2-fold greater in C alpha 12 cells than in L cells, while RAB10 cells lacked any induction of AP in response to CPT-cAMP. Northern blot and solution hybridization analyses of AP mRNA showed that induced AP mRNA levels were comparable in C alpha 12 and in L cells. Western blot analysis demonstrated that AP protein levels were greater in C alpha 12 cells and suggested that the increased AP protein level resulted from either increased stability of the AP protein or increased rate of translation of the AP mRNA. In contrast, Northern blot analysis of the RAB10 cells failed to detect AP mRNA after CPT-cAMP treatment and suggested that PKA is required for induction of AP mRNA. Stimulation of endogenous cAMP levels by treatment with prostaglandin E1 gave similar effects on AP activity as those seen with CPT-cAMP. These results indicate that cellular levels of PKA can determine the magnitude of cellular response to hormonal stimulation and also suggest that PKA can regulate AP gene expression at both the level of the AP mRNA and AP protein.
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PMID:Cellular concentrations of protein kinase A modulate prostaglandin and cAMP induction of alkaline phosphatase. 131 34

Calcium chloride-extracted histones were prepared from nuclei of the slime moulds, Physarum polycephalum and Dictyostelium discoideum, and phosphorylation by purified preparations of cyclic AMP-dependent protein kinase (cAMP-d PK) and growth-associated H1 histone kinase (HKG) examined and compared. Among the major histone fractions and other proteins in the two preparations, the H1 histones from both organisms were found to be effective and exclusive substrates for HKG. cAMP-d PK, which phosphorylates mammalian H1 histone and certain, in particular H2B, of the mammalian core histones, phosphorylated several of the core histones from both slime moulds but did not phosphorylate H1 histone from either. The slime mould H1s remained ineffective substrates for cAMP-d PK even after extensive alkaline phosphatase treatment of the histone preparations. Additional studies demonstrated that the lack of slime mould H1 phosphorylation by cAMP-d PK was not due to competition of the H1 molecules with the core histones for the kinase. Our studies suggest that H1 histones from these organisms, whilst clearly containing sites for phosphorylation by HKG, apparently lack phosphorylation sites recognised by cAMP-d PK. Thus, the mediation of specific nuclear functions by cAMP-dependent phosphorylation of H1 in higher organisms may not occur or be required in these lower eukaryotes.
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PMID:The lysine-rich H1 histones from the slime moulds, Physarum polycephalum and Dictyostelium discoideum lack phosphorylation sites recognised by cyclic AMP-dependent protein kinase in vitro. 132 Oct 59

We have measured the activity of the n type K+ channel present in human (Jurkat) T lymphocytes using the patch clamp technique in the whole-cell configuration. We report that protein kinase A (PKA) and protein kinase C (PKC) modulate, in a dual manner, the K+ conductance in these cells. Activation of PKA decreases the amplitude of the current, as previously reported (Bastin, B., Payet, M. D., and Dupuis, G. (1990) Cell. Immunol. 128, 385-399), and this is also the case for 12-O-tetradecanoylphorbol-13-acetate-dependent activation of PKC. In contrast, inhibitors of PKC (H7, staurosporine, polymixin B, and anti-PKC antibody) increase the current amplitude. Of importance, down-regulation of PKC or its inhibition prevented the PKA-dependent inhibition of the K+ channels. Addition of alkaline phosphatase via the patch pipette increased the K+ conductance under basal conditions and reversed the inhibition produced by PKA. The dual modulation of K+ channels in Jurkat T cells is in agreement with the presence of consensus sequences in the primary structure of the n type K+ channel.
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PMID:Dual regulation of the n type K+ channel in Jurkat T lymphocytes by protein kinases A and C. 132 19

In a previous study [Shaw, C., Pasqualotto, B. and Lanius, R.A., Mol. Neuropharmacol., in press] we have shown that phosphorylation and dephosphorylation actions of protein kinase and alkaline phosphatase lead to decreases or increases in the number of GABAA and AMPA receptors in adult rat neocortex. Using the same in vitro cortical slice preparation, we have now examined the role of these enzymes in regulating GABAA and AMPA receptors at different stages of postnatal development. GABAA receptors were labelled with [3H]SR95531 [Shaw, C. and Scarth, B.A., Mol. Brain Res., 11 (1991) 273-282]; AMPA receptors were labelled with [3H]CNQX [Lanius, R.A. and Shaw, C., Mol. Brain Res., 15 (1992) 256-262]. At postnatal day 14, GABAA receptors showed a decrease in binding in response to alkaline phosphatase treatment as opposed to an increase in binding observed in response to protein kinase treatment. Similar effects were observed for AMPA receptors at 20 days of age. The direction of regulation following the enzyme treatments were opposite to those observed in the adult cortex for both receptor populations. These fundamental changes in the enzymatic nature of regulation for such key inhibitory and excitatory receptor populations in cortex may signal an important role for age-dependent kinases and phosphatases in the events leading to modifications in neuronal function during postnatal development.
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PMID:Reversible kinase and phosphatase regulation of brain amino acid receptors in postnatal development. 133 48

We have previously demonstrated that the catalytic sub-unit of protein kinase A can catalyse a potent activation of partially purified Type V cyclic GMP-specific phosphodiesterase activity (Burns et al., 1992, Biochem. J. 283, 487-491). We now demonstrate that this phosphodiesterase most likely has a sub-unit mass of 90kDa, based upon 32P-cyclic GMP photo-affinity labelling, that activation of the phosphodiesterase does not require the prior binding of cyclic GMP to the phosphodiesterase, and that alkaline phosphatase can reverse the protein kinase A-dependent activation of phosphodiesterase activity. Zaprinast is a mixed inhibitor of non-activated cyclic GMP phosphodiesterase activity. However, inhibition of the protein kinase A-activated phosphodiesterase is competitive. These results suggest that protein kinase A can modulate the inhibitory effects of zaprinast via perturbations of a non-catalytic binding site.
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PMID:Interaction of the catalytic subunit of protein kinase A with the lung type V cyclic GMP phosphodiesterase: modulation of non-catalytic binding sites. 133 65

Fibrinogen was purified from five patients admitted for hip-replacement surgery the day before (day 0), the day after (day 2) and and one week after the operation (day 8). The behaviour of each patient's three fibrinogens was compared in thrombin gelation assays and plasmin degradation experiments to investigate whether the reported increase in protein-bound phosphate at day 2 and day 8 had any effect on the functional behaviour of fibrinogen as has been demonstrated in vitro. It was found that the thickness of the fibrin fibres produced by thrombin increased markedly at day 2 and declined thereafter. Susceptibility to plasmin appeared to decrease post-operatively by 50% and remained at that level on day 8 despite the phosphate content returning to normal. This has also been shown for fibrinogen phosphorylated in vitro. We conclude, after testing the fibrinogens with and without alkaline phosphatase pretreatment, that our data most resemble the published findings for in vitro phosphorylation of fibrinogen by casein kinase II.
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PMID:Increased phosphate content of fibrinogen in vivo correlates with alteration in fibrinogen behaviour. 134 Oct 57


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