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

---

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

The interaction between pyridoxal 5'-phosphate and the convertible serine of glycogen phosphorylase has been investigated by using: specific interconverting enzymes, phosphorylase kinase and phosphorylase phosphatase; effectors, glucose and glucose 6-phosphate; and a protein kinase and trypsin. Both phosphorylase kinase and phosphorylase phosphatase utilized the native protein while having little influence on the apoprotein. Removal of a peptide containing the critical serine residue gave phosphorylase b' from which the pyridoxal 5'-phosphate in phosphorylase has an important effect on enzymic interconversion.
...
PMID:Pyridoxal phosphate-dependent conformational states of glycogen phosphorylase as probed by interconverting enzymes. 16 24

We have demonstrated previously that cultured rat ovarian granulosa cells synthesize and secrete apoE, and this production of apoE is increased by agents that stimulate protein kinase A (cyclic AMP-dependent enzyme) (for example, cholera toxin) and protein kinase C (Ca2+/phospholipid-dependent enzyme) (for example, 12-O-tetradecanoylphorbol-13-acetate, a phorbol ester). In the studies presented in this report, we have examined the effect of changes in cell cholesterol synthesis on the production of apoE by rat ovarian granulosa cells. Mevinolin, an inhibitor of hydroxymethylglutaryl (HMG)-CoA reductase (the rate-limiting enzyme in cholesterol synthesis), and 4,4,10 beta-trimethyl-trans-decal-3 beta-ol, an inhibitor of squalene cyclization, both attenuate the cholera toxin or 12-O-tetradecanoylphorbol-13-acetate stimulation of granulosa cell apoE secretion and apoE mRNA content in a dose-responsive manner. The inhibitory effect of mevinolin is reversed by the concomitant administration of mevalolactone, which provides the cells with the product of the reaction catalyzed by HMG-CoA reductase. Steroidogenesis per se has no effect on apoE production. Aminoglutethimide, which blocks the rate-limiting step in steroidogenesis, has no effect on apoE or apoE mRNA. The data indicate that products of HMG-CoA reductase (isoprenes, cholesterol and/or cholesterol metabolites) are required along with stimulators of protein kinases A and C, to regulate ovarian granulosa cell apoE production.
...
PMID:Rat granulosa cell apolipoprotein E secretion. Regulation by cell cholesterol. 277 96

When hepatocytes were cultured for 24 h in the presence of forskolin (10(-4) mol l-1) or isobutylmethylxanthine (IBMX, 10(-3) mol l-1), the intracellular cAMP concentration peaked (320-380 pmol mg-1 protein) after 10-20 min of culture. This increase was accompanied by a decrease in the secretion of triacylglycerol, cholesterol and apoprotein B associated with VLDL. After 4 h cAMP levels had returned almost to basal values but the inhibition of VLDL secretion persisted. There was a small intracellular accumulation of triacylglycerol but not of apoprotein B. Addition of forskolin and IBMX together led to a further increase in intracellular cAMP and a further suppression of VLDL output. Similar effects on the secretion of VLDL were also observed after addition of Bt2cAMP. Exposure of cell cultures to glucagon (10(-7) mol l-1) for only 10 min raised cellular cAMP levels to > 200 pmol mg-1 protein, and suppressed VLDL secretion during the next 24 h to < 40% of control. All of the substances tested inhibited de novo synthesis of fatty acids but had little or no effect on cholesterol synthesis and did not inhibit oleate esterification to triacylglycerol. The cAMP-dependent protein kinase antagonist Rp-cAMPS prevented suppression of VLDL triacylglycerol secretion induced by glucagon (10(-7) mol l-1) and abolished glucagon-induced ketogenesis. Rp-cAMPS also inhibited Bt2cAMP (7.5 x 10(-6) mol l-1)-induced suppression of VLDL secretion and enhancement of ketogenesis. It is concluded that rat hepatic VLDL metabolism can be regulated by cAMP and cAMP-dependent protein kinases, and that the initial transient rise in cellular cAMP levels induced by glucagon is sufficient to maintain a long-term inhibitory effect on assembly and secretion of VLDL.
...
PMID:Regulation of VLDL secretion in primary culture of rat hepatocytes: involvement of cAMP and cAMP-dependent protein kinases. 820 83

The mechanisms for regulating platelet HDL3 binding sites were investigated. HDL3 binding was rapid (T(1/2) association=4 minutes) and completely reversible (T(1/2) dissociation=14.5 minutes) at 4 degrees C, 22 degrees C, and 37 degrees C, and kinetic analysis yielded forward and reverse constants of 7.3x10(-4) x s(-1) and 7.13x10(3) x s(-1) x M(-1), respectively. Nevertheless, neither inhibitors of binding sites recycling or of pinocytosis, such as ammonium chloride, chloroquine, monensin, colchicine, and sodium azide, modified the binding characteristics. Moreover, when platelets were loaded with cholesterol, binding sites were not regulated (up or down). However, when exposed to high concentrations of HDL3 (1.5 g/L), apoE-free HDL (1.5 g/L), HDL2 (0.5 g/L), apoE-rich HDL (0.5 g/L), and VLDL (0.3 g/L) there was rapid downregulation of the number of binding sites in isolated permeabilized platelets, as shown by the reduction of Bmax to 66%, 58%, 45%, 53%, and 51%, respectively. Downregulation was rapid, reversible, and dose and time dependent. In contrast, LDL (up to 2.0 g/L), IDL (up to 0.1 g/L), and chylomicrons (up to 0.5 g/L) had no effect. Protein kinase C inhibitors (150 nmol/L staurosporine, 100 micromol/L H-7, and 10 nmol/L bisindolylmaleimide) inhibited downregulation up to 62% (as average value). The role of the PKC activation in regulating the activity of HDL3 binding sites also was analyzed by determining the cytosol-to-membrane translocation of enzymatic activity. Downregulation mediated by HDL3 rapidly translocated PKC activity (21% +/- 11 of total PKC activity was membrane-associated in control platelets vs. 55+/-8% in downregulated platelets, mean+/-SEM, n=3). However, agents that block sequestration (0.30 g/L, concanavalin A), and other protein kinase inhibitors, such a cAMP-dependent protein kinase inhibitors (1 micromol/L, PKI), and beta2-adrenergic receptor kinase inhibitors (100 nmol/L, heparin) had no effect. The results show that neither endocytotic response nor cholesterol-dependent mechanisms participate in the modulation of platelet HDL3 binding sites. However, a new regulatory mechanism that involves PKC-dependent downregulation of the number of binding sites may be an important pathway to regulate the thrombogenicity of lipoproteins and their effects on platelet reactivity.
...
PMID:Mechanisms for regulating platelet high density lipoprotein type3 binding sites: evidence that binding sites are downregulated by a protein kinase C-dependent mechanism. 1021 79

Light-dependent activation of thylakoid protein phosphorylation regulates the energy distribution between photosystems I and II of oxygen-evolving photosynthetic eukaryotes as well as the turnover of photosystem II proteins. So far the only known effect of light on the phosphorylation process is the redox-dependent regulation of the membrane-bound protein kinase(s) activity via plastoquinol bound to the cytochrome bf complex and the redox state of thylakoid dithiols. By using a partially purified thylakoid protein kinase and isolated native chlorophyll (chl) a/b light-harvesting complex II (LHCII), as well as recombinant LHCII, we find that illumination of the chl-protein substrate exposes the phosphorylation site to the kinase. Light does not activate the phosphorylation of the LHCII apoprotein nor the recombinant pigment-reconstituted complex lacking the N-terminal domain that contains the phosphothreonine site. The suggested light-induced conformational change exposing the N-terminal domain of LHCII to the kinase is evidenced also by an increase in its accessibility to tryptic cleavage after light exposure. Light activates preferentially the trimeric form of LHCII, and the process is paralleled by chl fluorescence quenching. Both phenomena are slowly reversible in darkness. Light-induced exposure of the LHCII N-terminal domain to the endogenous protein kinase(s) and tryptic cleavage occurs also in thylakoid membranes. These results demonstrate that light may regulate thylakoid protein phosphorylation not only via the signal transduction chain connecting redox reactions to the protein kinase activation, but also by affecting the conformation of the chl-protein substrate.
...
PMID:Regulation of thylakoid protein phosphorylation at the substrate level: reversible light-induced conformational changes expose the phosphorylation site of the light-harvesting complex II. 1039 85

Phototropism, the bending response of plant organs to or away from a directional light source, is one of the best studied blue light responses in plants. Although phototropism has been studied for more than a century, recent advances have improved our understanding of the underlying signaling mechanisms involved. The NPH1 gene of Arabidopsis thaliana encodes a blue light-dependent autophosphorylating protein kinase with the properties of a photoreceptor for phototropism. NPH1 apoprotein noncovalently binds FMN to form the holoprotein nph1. The N-terminal region of the protein contains two LOV (light, oxygen, or voltage) domains that share homology with sensor proteins from a diverse group of organisms. These include the bacterial proteins NIFL and AER, both of which bind FAD, and the phy3 photoreceptor from Adiantium capillus-veneris. The LOV domain has therefore been proposed to reflect a flavin-binding site, regulating nph1 kinase activity in response to blue light-induced redox changes. Herein we demonstrate that the LOV domains of two nph1 proteins and phy3 bind stoichiometric amounts of FMN when expressed in Escherichia coli. The spectral properties of the chromopeptides are similar to the action spectrum for phototropism, implying that the LOV domain binds FMN to function as a light sensor. Thus, our findings support the earlier model that nph1 is a dual-chromophoric flavoprotein photoreceptor regulating phototropic responses in higher plants. We therefore propose the name phototropin to designate the nph1 holoprotein.
...
PMID:LOV (light, oxygen, or voltage) domains of the blue-light photoreceptor phototropin (nph1): binding sites for the chromophore flavin mononucleotide. 1041 52

Cytochrome P4502E1 (CYP2E1) plays a key role in the metabolism of numerous drug substrates, mostly in mammalian liver. Both the apoprotein and mRNA levels are increased in response to interleukin 4 (IL-4) in primary human hepatocyte cultures. We developed a human hepatoma cell model that faithfully reproduces the responsiveness of the CYP2E1 gene to IL-4 at least in part through transcriptional activation, upon treatment with 150 U/ml of IL-4. As expected, IL-4 induced tyrosine phosphorylation of the STAT6 transcription factor, an effect prevented by the tyrosine kinase inhibitor tyrphostin A25. However, this inhibitor as well as genistein (another inhibitor of tyrosine kinases) had no effect on the IL-4 induction of CYP2E1. Similarly, protein kinase A activators (forskolin and dibutyryl-cAMP) and inhibitor (H89) did not influence the response to IL-4. However, PKC inhibitors (H7 and calphostin C) strongly blocked any induction of the gene, as well as the IL-4-dependent translocation of PKCS. Taken together, our results show that IL-4 coordinately induces CYP2E1 transcription, mRNA and apoprotein levels in human hepatoma cells in a PKC-dependent manner, potentially through the activity of the PKCzeta isoform.
...
PMID:The induction of the human hepatic CYP2E1 gene by interleukin 4 is transcriptional and regulated by protein kinase C. 1110 Oct 4

The protein kinase ZAP-70 is involved in T-cell activation, and interacts with tyrosine-phosphorylated peptide sequences known as immunoreceptor tyrosine activation motifs (ITAMs), which are present in three of the subunits of the T-cell receptor. We have studied the tandem SH2 (tSH2) domains of ZAP-70, by both X-ray and NMR. Here, we present the crystal structure of the apoprotein, i.e., the tSH2 domain in the absence of ITAM. Comparison with the previously reported complex structure reveals that binding to the ITAM peptide induces surprisingly large movements between the two SH2 domains and within the actual binding sites. The conformation of the ITAM-free protein is partly governed by a hydrophobic cluster between the linker region and the C-terminal SH2 domain. Our data suggest that the two SH2 domains are able to undergo large interdomain movements. The proposed relative flexibility of the SH2 domains is further supported by the finding that no NMR signals could be detected for the two helices connecting the SH2 domains; these are likely to be broadened beyond detection due to conformational exchange. It is likely that this conformational reorientation induced by ITAM binding is the main signaling event activating the kinase domain in ZAP-70. Another NMR observation was that the N-terminal SH2 domain could bind tetrapeptides derived from the ITAM sequence, apparently without the need to interact with the C-terminal domain. In contrast, the C-terminal domain has little affinity for tetrapeptides. The opposite situation is true for binding to plain phosphotyrosine, where the C-terminal domain has a higher affinity. Distinct features in the crystal structure, showing the interdependence of both domains, explain these binding data.
...
PMID:Crystal structure and NMR studies of the apo SH2 domains of ZAP-70: two bikes rather than a tandem. 1245 Mar 81

Midkine (MK), a heparin-binding growth factor, suppresses apoptosis of embryonic neurons in culture, induced by serum deprivation. Receptor-type protein tyrosine phosphatase zeta (PTP zeta) is a chondroitin sulfate proteoglycan with a transmembrane domain and intracellular tyrosine phosphatase domains. The activity of MK was abolished by digestion with chondroitinase ABC, or addition of the antibody to PTP zeta, while digestion with heparitinase showed no significant effect. These results suggested that the survival-promoting signal of MK was received by a receptor complex containing PTP zeta. Low density lipoprotein receptor-related protein (LRP) has been identified as another component of the signaling receptor. Ectodomains of two related proteins expressed on neurons, namely LRP6 and apoE receptor 2, were FLAG-tagged and examined for MK binding, using MK-agarose column. Both the ectodomains were found to exhibit calcium-dependent binding to MK. These proteins may participate in MK signaling in certain cases. The survival-promoting activity of MK was abolished by PP1, an inhibitor of src protein kinase, pertussis toxin, an inhibitor of G protein-linked signaling and sodium orthovanadate, an inhibitor of PTPs.
...
PMID:Receptor-type protein tyrosine phosphatase zeta as a component of the signaling receptor complex for midkine-dependent survival of embryonic neurons. 1257 68

Over the years, the vascular protective role of apolipoprotein (apo) E has been attributed to the ability of apoE to induce cholesterol efflux from macrophage foam cells and its transport of extrahepatic cholesterol to the liver for excretion out of the body. Recently, apoE has been shown to protect against vascular disease by additional mechanisms that are independent of its cholesterol transport functions. This review summarizes data demonstrating apoE binding to specific cell surface receptors and proteoglycans in smooth muscle cells triggers distinct signalling pathways that result in inhibition of cell migration, proliferation, and excessive extracellular matrix deposition. apoE binding to the low density lipoprotein receptor-related protein is responsible for inhibition of cell migration, due to the induction of cyclic AMP accumulation and protein kinase A activation. apoE inhibition of cell proliferation is mediated by its binding to proteoglycans and the resulting activation of inducible nitric oxide synthase. apoE also inhibits excessive extracellular matrix protein synthesis. The receptor responsible for this latter apoE function remains to be identified.
...
PMID:Distinct signaling mechanisms for apoE inhibition of cell migration and proliferation. 1563 9


1 2 3 4 Next >>

---