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)

Transcriptional activation of the murine Cyp1a-1 (cytochrome P(1)450) gene by inducers such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (dioxin) requires the aromatic hydrocarbon (Ah) receptor and the interaction of an inducer-receptor complex with one or more of the Ah-responsive elements (AhREs) located about 1 kb upstream from the transcriptional initiation site. We find that treatment of mouse hepatoma Hepa-1 cells with 2-aminopurine, an inhibitor of protein kinase activity, inhibits CYP1A1 mRNA induction by TCDD as well as the concomitant increase in CYP1A1 enzyme activity. Formation of DNA-protein complexes between the Ah receptor and its AhRE target is also inhibited by 2-aminopurine, as determined by gel mobility shift assays. Phosphorylation is required for the formation of Ah receptor-specific complexes, since in vitro dephosphorylation of nuclear extracts from TCDD-treated Hepa-1 cells abolishes the capacity of the Ah receptor to form specific complexes with its cognate AhRE sequences. To determine whether any one of several known protein kinases was involved in the transcriptional regulation of the Cyp1a-1 gene, we treated Hepa-1 cells with nine other protein kinase inhibitors prior to induction with TCDD; nuclear extracts from these cells were analyzed for their capacity to form specific DNA-protein complexes. Only extracts from cells treated with staurosporine, a protein kinase C inhibitor, were unable to form these complexes. In addition, staurosporine completely inhibited CYP1A1 mRNA induction by TCDD. Depletion of protein kinase C by prolonged treatment with phorbol ester led to the complete suppression of CYP1A1 mRNA induction by TCDD. We conclude that (i) phosphorylation is necessary for the formation of a transcriptional complex and for transcriptional activation of the Cyp1a-1 gene; (ii) the phosphorylation site(s) exists on at least one of the proteins constituting the transcriptional complex, possibly the Ah receptor itself; and (iii) the enzyme responsible for the phosphorylation is likely to be protein kinase C.
...
PMID:Dioxin-dependent activation of murine Cyp1a-1 gene transcription requires protein kinase C-dependent phosphorylation. 131 72

Stimulation of protein kinase C (PKC) by phorbol ester (PMA) was reported previously to increase total binding of the peptide in whole rat pituitary cells. The effect could be obtained in cells from intact, not from spayed animals, suggesting a different level of spontaneous phosphorylation in both conditions. In the present work, endogenous PKC was desensitized in pituitary cells sampled from intact or 3 weeks castrated male rats and maintained in primary culture. Desensitization was induced by overnight incubation with 1 microM PMA. The maximum number of plasma membrane LHRH receptors (Bmax) present on cells from in intact animals was higher (+ 98 +/- 9%) when binding was performed at 0.5 degrees C instead of 21 degrees C as already observed in non PKC-desensitized cells. PMA (100 nM) was ineffective to increase Bmax, suggesting effectiveness of enzyme desensitization. In contrast, ionomycin 1 microM increased Bmax (53 +/- 10%). This increment was inhibited by W7, a calmodulin inhibitor, with an IC50 = 1 +/- 0.35 10(-6) M. No temperature dependency of the Bmax was observed in cells from castrated rats as already shown in the absence of PKC desensitization. Under these conditions, a Bmax decrease of 34 +/- 6% and 36.5 +/- 7.5% respectively was observed in the presence of H7, a PKC inhibitor, or of W7 (IC50 = 1 +/- 0.5 10(-5) M and IC50 = 0.8 +/- 0.2 10(-6) M). We conclude that a Ca2+ calmodulin dependent protein kinase rather than PKC itself is responsible for unmasking LHRH receptors.
...
PMID:A Ca2+ calmodulin dependent kinase rather than protein kinase C is involved in up-regulation of the LHRH receptor. 131 37

Inositol 1,4,5-trisphosphate (IP3) releases internal stores of calcium by binding to a specific membrane receptor which includes both the IP3 recognition site as well as the associated calcium channel. The IP3 receptor is regulated by ATP, calcium, and phosphorylation by protein kinase A, protein kinase C, and calcium/calmodulin-dependent protein kinase II. Its cDNA sequence predicts at least two consensus sequences where nucleotides might bind, and direct binding of ATP to the IP3 receptor has been demonstrated. In the present study, we demonstrate autophosphorylation of the purified and reconstituted IP3 receptor on serine and find serine protein kinase activity of the IP3 receptor toward a specific peptide substrate. Several independent purification procedures do not separate the IP3 receptor protein from the phosphorylating activity, and many different protein kinase activators and inhibitors do not identify protein kinases as contaminants. Also, renaturation experiments reveal autophosphorylation of the monomeric receptor on polyvinylidene difluoride membranes.
...
PMID:Autophosphorylation of inositol 1,4,5-trisphosphate receptors. 131 30

We investigated the regulatory mechanisms of endothelin (ET)-1 production in cultured rat mesangial cells (MC), with a special focus on the roles of protein kinase A (PKA)- and protein kinase C (PKC)-mediated signaling systems. Vasoactive agents and growth promoting factors, including platelet-derived growth factor, vasopressin and thrombin, which act through receptors coupled to the phospholipase C-mediated signaling system, as well as phorbol ester and fetal calf serum stimulated ET-1 production. This effect was attenuated in PKC-depleted or H-7 (a PKC inhibitor) treated MC. On the other hand, an increase in intracellular cyclic AMP by forskolin or beta-adrenergic agonist, isoproterenol, which act as anti-mitogenic agents, inhibited serum-stimulated ET-1 production. In addition this effect was mimicked by the addition of 8-bromo-cyclic AMP to the medium. The effect of isoproterenol was abolished by propranolol. H-8, a PKA inhibitor, attenuated the inhibitory effect of forskolin. These findings suggest that ET-1 production in MC is regulated by interaction of both positive and negative signals mediated by PKC- and PKA-dependent mechanisms.
...
PMID:Regulation of endothelin-1 production in cultured rat mesangial cells. 131 23

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.
...
PMID:Stimulation by growth hormone of MAP kinase activity in 3T3-F442A fibroblasts. 131 28

The effects of serine phosphorylation on the DNA cleavage/religation equilibrium of topoisomerase II and the sensitivity of the enzyme to antineoplastic drugs were characterized. Both casein kinase II and protein kinase C were used for these studies. Each kinase incorporated a maximum of approximately 1.4 phosphate molecules per homodimer of topoisomerase II. When the enzyme was incubated with both kinases simultaneously, phosphate incorporation increased to approximately 2.6 molecules/homodimer. In the absence of antineoplastic drugs, phosphorylation had only a slight effect on the DNA cleavage/religation equilibrium of topoisomerase II. However, in the presence of etoposide or 4'-(9-acridinylamino)methane-sulfon-m-anisidide, phosphorylation attenuated the ability of drugs to stabilize enzyme-DNA cleavage complexes. Levels of drug-induced DNA cleavage products decreased approximately 33% following phosphorylation of topoisomerase II by casein kinase II, approximately 17% following modification by protein kinase C, and approximately 50% following simultaneous phosphorylation of the enzyme by both kinases. This latter 50% reduction in DNA cleavage products correlated with an approximately 2-fold increase in the apparent first order rate constant for DNA religation mediated by simultaneously modified topoisomerase II. These results strongly suggest that the sensitivity of topoisomerase II toward antineoplastic drugs can be modulated by altering the phosphorylation state of the enzyme.
...
PMID:Phosphorylation of topoisomerase II by casein kinase II and protein kinase C: effects on enzyme-mediated DNA cleavage/religation and sensitivity to the antineoplastic drugs etoposide and 4'-(9-acridinylamino)methane-sulfon-m-anisidide. 131 38

The activities of Ca2+/calmodulin (CaM)-dependent, Ca2+/phospholipid-dependent, and cyclic AMP-dependent protein kinases (CaM-KII, PKC, and PKA, respectively) were determined in rat brains after global ischemia. Both CaM-KII and PKC activities were significantly depressed in both hippocampal and cerebral cortical regions of ischemic animals, whereas no change was detected in PKA activity. The loss of CaM-KII activity was more dramatic and more sustained than the loss of PKC activity and correlated with the duration of ischemia. These decreases in enzyme activity were found in both supernatant and pellet fractions from crude homogenates. When the supernatant and pellet were analyzed for the amount of CaM-KII 50-kDa protein, a significant decrease was detected in supernatant fractions that paralleled a gain in the amount of CaM-KII in the pellet. Thus, the loss of CaM-KII activity in the supernatant can be explained by translocation of the enzyme to the pellet. Whether inactivation of CaM-KII occurs during or after the enzyme translocates from the supernatant to the pellet is unknown. Our results indicate that loss in CaM-KII activity parallels neuronal damage associated with ischemia; down-regulation of CaM-KII activity coincided with translocation of the enzyme to the particulate fraction, and it is proposed that this may be, in fact, a mechanism for controlling excessive CaM-KII phosphorylation.
...
PMID:Ischemia-induced translocation of Ca2+/calmodulin-dependent protein kinase II: potential role in neuronal damage. 131 52

Parathyroid hormone action on renal proximal tubule function involves phospholipase C/protein kinase C as well as adenylate cyclase/protein kinase A mediated regulatory pathways. Tissue culture experiments suggest that low concentrations of PTH affect preferentially the phospholipase C/protein kinase C pathway. In vivo, both regulatory cascades are probably involved in the regulation of proximal tubule function. It is not clear at present whether the two intracellular pathways are linked to one or two PTH receptors. A polarized distribution of PTH receptor(s) involving different second messengers appears possible in proximal tubule epithelial cells. High-affinity (Kd 10(-11)-10(-12) M) PTH receptors in the range of circulating PTH concentrations in vivo remain to be identified. Structural and functional characterization of PTH receptors as well as of the PTH-sensitive intracellular mediators and transport systems form the basis for a better understanding of PTH-dependent regulation of proximal tubule function.
...
PMID:Parathyroid hormone receptors in control of proximal tubule function. 131 47

Herpes simplex virus type 1 (HSV-1) establishes latent infections in neurons of sympathetic and sensory ganglia in humans, and reactivation of latent virus results in recurrent disease. Previously, we reported establishment of latent HSV-1 infections in neuronal cultures derived from rats, monkeys, and humans; reactivation occurs following nerve growth factor (NGF) deprivation. The processes controlling HSV latency are not understood. Using the in vitro neuronal latency system, we have shown that latent HSV-1 reactivated in response to stimulation of at least two second-messenger pathways. Stimulation of cAMP-dependent pathways by several mechanisms or activation of protein kinase C by phorbol myristate acetate (PMA) resulted in reactivation of latent HSV-1. The reactivation kinetics following treatment with activators of protein kinase A and C were accelerated compared with those following NGF deprivation. 2-Aminopurine, which inhibits NGF-stimulated protein kinases and other classes of protein kinases, but does not effect protein kinase A or C, blocked reactivation produced by NGF deprivation or treatment with a cAMP analog, but not reactivation by PMA treatment. These results demonstrate that latent HSV-1 reactivates in neurons in vitro in response to activation of second-messenger pathways.
...
PMID:Activation of second-messenger pathways reactivates latent herpes simplex virus in neuronal cultures. 131 58

Changes in the activity of the brush-border Na-H antiporter are accompanied by parallel changes in the activity of the Na-HCO3 cotransporter. Adenosine 3',5'-cyclic monophosphate (cAMP) and calmodulin inhibit the Na-H antiporter, whereas protein kinase C (PKC) stimulates it. We hypothesized that cAMP, calmodulin, and PKC should have similar effects on the Na-HCO3 cotransporter activity. Phosphorylated renal basolateral membranes were treated with either cAMP, calmodulin, or phorbol ester. cAMP, 1 microM, inhibited HCO3-dependent 22Na uptake without affecting 22Na uptake in presence of gluconate, suggesting that cAMP inhibits Na-HCO3 cotransporter activity without altering diffusive 22Na uptake. The effect of cAMP to inhibit the Na-HCO3 cotransporter could also be elicited by the catalytic subunit of cAMP, and this inhibitory effect was prevented by the protein kinase A (PKA) inhibitor. Calmodulin (1 microM), in presence of Ca, also inhibited HCO3-dependent 22Na uptake in presence of HCO3, whereas 22Na uptake in the presence of gluconate was unchanged. The inhibitory effect of calmodulin on HCO3-dependent 22Na uptake was prevented by N-(4-aminobutyl)-5-chloro-2-naphthalene sulfonamide (W-13), an inhibitor of calmodulin. Phorbol 12-myristate 13-acetate and PKC stimulated Na-HCO3 cotransporter activity, whereas the inactive analogue, 4 alpha-phorbol, failed to elicit such a stimulation. Basolateral membranes displayed cAMP-dependent and Ca-dependent protein kinase activities. Thus PKA and Ca-dependent protein kinases regulate the activity of the Na-HCO3 cotransporter and suggest that hormones that act through these systems modulate the activity of the Na-HCO3 cotransporter.
...
PMID:Regulation of the renal Na-HCO3 cotransporter by cAMP and Ca-dependent protein kinases. 131 5


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---