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 initial step in TSH action reflects binding of the hormone to specific receptor sites on the plasma membrane. Such binding has been studied using plasma membranes, homogenates, isolated thyroid cells grown in culture, and thyroid slices. 3-H- and iodinated TSH preparations have been used; the latter have been prepared using both chloramine-T and lactoperoxidase. Some of the discrepancies reported in the literature might reflect the different thyroid and hormone preparations and the variable incubation conditions which have been used. In general, good correlation exists between binding of TSH and activation of adenylate cyclase in thyroid plasma membranes. Data is reviewed related to activation of protein kinase in intact thyroid cells by TSH. Although there is impressive evidence for cyclic AMP mediation of effects of TSH on the thyroid, some data that are inconsistent with this concept are considered, especially in relationship to 32-P incorporation into phospholipid. The role of cyclic GMP in thyroid function is discussed.
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PMID:Thyroid-stimulating hormone and cyclic adenosine 3',5'-monophosphate in the regulation of thyroid gland function. 16 59

The peptide compositions of rabbit skeletal- and canine cardiac-muscle sarcoplasmic reticulum preparations have been compared by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. The cardiac preparations contain many proteins in addition to the 105 000 dalton peptide which has been previously identified as the Ca2+ stimulated ATPase. Four peptide components iodinated in the presence of either free or Sepharose 4B-bound lactoperoxidase have molecular weights of 130 000 (component I), 105 000 (component II), 52 000 (component III) and 47 000 (component IV). Comparison of the labelling patterns in the presence of the detergent Triton X-100 suggests that components I, III and IV have part of their peptide internally located. Although part of component II is externally accessible to free lactoperoxidase, its iodination is decreased by Triton X-100. Iodination of phospholamban, the 22 000 dalton substrate for cyclic AMP-dependent protein kinase, was not observed under the conditions investigated.
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PMID:Lactoperoxidase-coupled iodination of cardiac sarcoplasmic reticulum proteins. 90 8

When HL-60 cells were stimulated with histamine, a significant differentiation of the cells toward neutrophils was elicited. Histamine increased phagocytic activity, but it reduced myeloperoxidase activity of HL-60 cells. Histamine-induced differentiation in HL-60 cells was inhibited not only by H2 antagonists, such as cimetidine, ranitidine and famotidine, but also by an inhibitor of protein kinase A (A kinase), KT-5720. Histamine increased the cAMP level and A kinase activity in HL-60 cells; both increases preceded the cell differentiation. Histamine also enhanced phosphorylation of a 160 kD protein in HL-60 cells, while H2 antagonists and KT-5720 inhibited this phosphorylation. The results of the present study indicate that an activation of A kinase via H2 receptor stimulation may cause the phosphorylation of a 160 kD protein and that this phosphorylation is probably involved in the process leading to differentiation of HL-60 cells.
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PMID:Histamine-induced differentiation of HL-60 cells. The role of cAMP and protein kinase A. 132 60

Endocytosis in the chloride secreting epithelial cell line T84 was monitored by uptake of the fluid-phase markers FITC-dextran and horseradish peroxidase (HRP). Uptake of marker was inhibited by incubation of cells at 4 degrees C, consistent with an endocytic uptake. Although activation of the cAMP-dependent second messenger pathway has been shown to stimulate exocytosis in this cell line, it caused a 63% reduction in endocytosis as measured by uptake of fluid-phase markers. In contrast, the presence of the protein kinase C activator phorbol-myristate acetate (PMA) caused no significant reduction in the level of endocytosis compared to control, nor did it reverse the inhibitory effect of PKA activation. The data thus suggest that endocytosis in T84 cells is regulated through activation of protein kinase A, but not through activation of protein kinase C.
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PMID:Endocytosis is regulated by protein kinase A, but not protein kinase C in a secretory epithelial cell line. 137 55

A 96-well microtiter enzyme-linked immunosorbent assay (ELISA) for protein tyrosine kinases has been developed. This assay uses one of several substrates that are phosphorylated by tyrosine kinase, an antibody to phosphotyrosine, and a peroxidase-linked second antibody. Color development is monitored by a change in absorbance at 450 nm and is dependent upon time, enzyme, ATP, and substrate concentrations. Specificity of the ELISA for phosphotyrosine was shown by inhibition of binding of the anti-phosphotyrosine antibody with phenyl phosphate. Results obtained in the ELISA compared favorably with those obtained by direct phosphorylation of the substrate with [32P]ATP. Staurosporine and K252a, protein kinase inhibitors, showed titratable inhibition of tyrosine kinase activity. This assay is a rapid, nonradioactive alternative to traditional methodology and is also amenable to automation.
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PMID:A microtiter-based assay for the detection of protein tyrosine kinase activity. 170 96

An inhibitor of protein kinases, staurosporine (ssp), was found to affect the endocytic pathway of asialoglycoproteins subsequent to endocytosis in monolayer cultures of rat hepatocytes. The effect of 5 or 10 microM staurosporine on the internalization of a synthetic ligand (galBSA-HRP: bovine serum albumin exposing galactose, horseradish peroxidase conjugates) prebound to the cell surface was minimal. The presence of 5, 7, or 10 microM ssp during a 1-h chase period resulted in the ligand remaining in a low density (1.04-1.05 g/ml), nonlysosomal subcellular fraction in a Percoll gradient. The ligand, arrested by 7 microM ssp, was further processed to the lysosome during subsequent incubation in the absence of ssp. Cells maintained the ability to internalize ligand at 37 degrees C for 1 h in the presence of these concentrations of ssp. During a 1-h continuous uptake of 0-50 micrograms/ml nonlabeled ligand, the presence of 7 microM ssp did not cause any decrease in the amount of asialoglycoprotein receptor at the cell surface, which indicates receptor recycling occurred normally. These results suggest a possible involvement of protein kinase(s), which can be inhibited by ssp, in the delivery of endocytosed ligand to the lysosome, but not in ligand endocytosis and receptor recycling.
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PMID:An inhibitory effect of a protein kinase inhibitor, staurosporine, on delivery of endocytosed asialoglycoprotein to lysosome in monolayer culture of rat hepatocytes. 195 54

We reported previously that, following phosphorylation by cyclic AMP-dependent protein kinase, tyrosine hydroxylase in rat corpus striatal extracts is inactivated in a time-dependent and apparently irreversible fashion. Removal of low molecular weight substances from these extracts by gel filtration attenuates this inactivation. We tried to determine the identity of endogenous metabolites that promote inactivation of tyrosine hydroxylase under our experimental conditions. In the present study, we report that the reducing co-substrate tetrahydrobiopterin and its analogues promoted this irreversible inactivation. The concentration that produced a 50% loss of activity (at 20 min) of the phosphorylated enzyme was 0.7 microM and that for the unphosphorylated enzyme was 420 microM. Using enzyme purified from a rat pheochromocytoma, we found that tyrosine, alpha-methyl-p-tyrosine, and a 3-iodotyrosine protected the phosphorylated enzyme against the inactivation produced by tetrahydrobiopterin. Catecholamines (dopamine, norepinephrine, epinephrine, and some of their analogues) also nullified inactivation. In contrast, the product of the reaction, dihydroxyphenylalanine, failed to attenuate the inactivation process. We performed several studies to ascertain the mechanism of inhibition by tetrahydrobiopterin. We considered the possibility that it formed reactive free radicals that produced inhibition. Free radical scavengers, however, failed to block the inhibition produced by tetrahydrobiopterin. Superoxide dismutase, catalase, and peroxidase also failed to protect tyrosine hydroxylase against inactivation. Moreover, when the experiments were performed under anaerobic conditions, the inactivation process was unaffected. These results suggest that reactive oxygenated species were not required for inactivation by tetrahydrobiopterin.
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PMID:Inactivation of tyrosine hydroxylase by pterin substrates following phosphorylation by cyclic AMP-dependent protein kinase. 197 41

Monoclonal antibody YC10 showed specificity for the phosphorylated form of human, bovine and porcine glial fibrillary acidic proteins (GFAPs) and negligible reactivity towards the dephosphorylated form of the GFAPs. Analysis of species specificity and of the epitope, determined using synthetic phosphopeptides, indicated that this antibody recognized the local phosphorylation-site sequence Thr-phosphoSer-Ala-Ala-Arg-Arg (residues 7-12 of GFAP). Making use of this antibody we developed a non-radioactive method to measure protein kinase activities. After incubation of a protein kinase with non-radioactive ATP in ninety-six wells coated with the synthetic peptide Arg-Arg-Arg-Val-Thr-Ser-Ala-Ala-Arg-Arg-Ser-Cys (residues 3-13 of GFAP), the phosphorylated product was detected by using this mouse antibody and peroxidase-labeled goat anti-mouse IgG. This method proved to be equally as sensitive as the radioactive method for the measurement of protein kinase activities and was less affected by concentrations of ATP present in the reaction mixture.
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PMID:A monoclonal antibody to the phosphorylated form of glial fibrillary acidic protein: application to a non-radioactive method for measuring protein kinase activities. 202 46

We have demonstrated that anterior pituitary corticotropes can be identified cytochemically by their capacity to bind potent biotinylated analogs of CRH. In addition, 50-80% of corticotropes bind biotinylated arginine vasopressin (AVP). The percentage of CRH-bound cells is rapidly reduced after 1-h exposure to glucocorticoids. However, the rapid effects of glucocorticoids on AVP binding by corticotropes have not been tested. The first aim of this study was to examine the binding capacity of small and large corticotropes enriched to 90% by counterflow centrifugation. Biotinylated analogs of CRH or AVP were detected cytochemically on the cells by avidin-biotin-peroxidase complex protocols. At least 80% of the cells bound CRH after 1 day of culture. More large corticotropes bound AVP (93%) than small corticotropes (80%). AVP pretreatment of large corticotropes stimulated an increase in CRH-bound cells to over 90%, but it had no effect on CRH binding by small corticotropes. Corticosterone pretreatment (100 nM) for 10 min caused a 50% reduction in the percentage of cells that bound CRH and in the levels of ACTH released in response to biotinylated CRH. After 30 and 60 min of pretreatment, the percentages of CRH-bound cells were reduced by 75%, and ACTH levels remained low. No reduction in percentages of AVP-bound cells was evident at any time point after corticosterone pretreatment. These studies stimulated further tests based on previous reports that showed that AVP or its activated second messengers enhanced CRH binding. We reasoned that this potentiation might promote a recovery in CRH binding to corticosterone-inhibited cells. However, 1-h stimulation by AVP or activation of calcium channels (by Bay K 8644) or protein kinase-C by 12-O-tetradecanoyl-phorbol-13-acetate did not restore CRH binding. AVP evoked a partial recovery in ACTH release. Furthermore, Bay K and 12-O-tetradecanoyl-phorbol-13-acetate pretreatment effectively blocked the fast feedback effects of corticosterone on CRH-mediated ACTH release. Thus, these studies demonstrate that glucocorticoids rapidly inhibit CRH-receptor binding in a domain that is not affected by AVP potentiation of ACTH release. Perhaps they immobilize transport processes needed to bring unoccupied CRH receptors to the surface for binding and cytochemical detection.
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PMID:Rapid corticosterone inhibition of corticotropin-releasing hormone binding and adrenocorticotropin release by enriched populations of corticotropes: counteractions by arginine vasopressin and its second messengers. 215 74

Guniea-pig peritoneal eosinophils generated superoxide anions in response to opsonized zymosan, platelet activating factor, sodium fluoride, digitonin, phorbol ester and calcium ionophore, but were refractory to fMLP. These agonists did not stimulate release of eosinophil peroxidase. The phospholipase inhibitor, mepacrine, and the protein kinase inhibitor, trifluoperazine, were effective inhibitors of superoxide production. Activators of protein kinase C, such as exogenously added phorbol ester and endogenously derived diacylglycerol, stimulate superoxide production, which is therefore proposed to be via pathways dependent on phospholipase and protein kinase activity.
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PMID:Studies of cellular mechanisms for the generation of superoxide by guinea-pig eosinophils and its dissociation from granule peroxidase release. 217 98


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