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)

Ca2+-mobilizing receptor-induced inositol phospholipid hydrolysis has been studied in cultured endothelial cells (EC) from human aorta, pulmonary artery, and umbilical vein. It was shown that in EC the release of inositol phosphates can be stimulated by histamine, thrombin, serotonin, acetylcholine, carbachol, bradykinin, vasopressin, angiotensin II, platelet-activating factor (PAF), the thromboxane A2 mimetic, U46619, and prostaglandin E2. The most effective agonists were thrombin, histamine, and PAF, producing two- to five-fold increases in inositol phosphate level, and a 50-90% elevation of the level of inositol trisphosphate within 5 min. Effects of other agonists were smaller, although significant. Incubation of EC with histamine or PAF for 1 h resulted in a four- to eight-fold decrease of beta-adrenoreceptor density in the plasma membranes. The activity of isoproterenol-stimulated adenylate cyclase was depressed, and the degree of stimulation by isoproterenol was reduced. Similar effects were obtained after treatment of EC with the protein kinase C activator 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, suggesting a role of protein kinase C in receptor desensitization. It is concluded, that stimulation of inositol phospholipid hydrolysis, and, consequently, activation of protein kinase can cause receptor imbalance in human vascular endothelium. This mechanism may play a pivotal role in the pathogenesis of cardiovascular and pulmonary diseases.
...
PMID:Regulation of phosphoinositide turnover in endothelium from human pulmonary artery, aorta and umbilical vein. Antagonistic action on the beta-adrenoceptor coupled adenylate cyclase system. 254 21

Madin-Darby canine kidney cells (MDCK) are known to release free arachidonic acid and arachidonic acid metabolites (AA) in response to tumor-promoting phorbol esters, such as tetradecanoyl phorbol-13-acetate, and to agonists active at alpha 1-adrenergic and bradykinin B2 receptors. These experiments were conducted to define the role of Ca2+/phospholipid-dependent protein kinase (protein kinase C) activation in the stimulation of AA release, in the clonal isolate cell line MDCK-D1, by use of three inhibitors of protein kinase C, sphingosine, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), and staurosporine. We found that alpha 1-adrenergic- and bradykinin-stimulated [3H]AA release can be distinguished by differential dependence on protein kinase C; epinephrine-stimulated release was more dependent on protein kinase C activation than was bradykinin-stimulated release. The inhibition of bradykinin-stimulated AA release by sphingosine (20.2 +/- 6.1%) was substantially less than the inhibition observed for tetradecanoyl phorbol-13-acetate- (67.2 +/- 5.5%) and epinephrine-stimulated release (50.2 +/- 9.2%). These findings were confirmed by results using H-7 and staurosporine. The relative independence of bradykinin-stimulated AA release of protein kinase C was also demonstrated by the inability of phorbol ester-induced down-regulation of protein kinase C to eliminate bradykinin-stimulated AA release. The inhibition of alpha 1-adrenergic receptor-mediated AA release by sphingosine, H-7, and staurosporine was not due to a change in receptor number or affinity. Analysis of the products comprising [3H]AA release indicated that treatment with sphingosine did not change the composition of the released AA (34-48% prostaglandin E2, 17-27% free arachidonic acid, and 25-51% unidentified metabolites). These results indicate that two different types of hormone receptors in the same cell type can promote AA release by mechanisms that differ in their dependence on protein kinase C. The protein kinase C-dependent mechanism may represent protein kinase C-mediated activation of phospholipase A2.
...
PMID:Defining the role of protein kinase C in epinephrine- and bradykinin-stimulated arachidonic acid metabolism in Madin-Darby canine kidney cells. 254 87

BALB/c 3T3 cells infected with a temperature-sensitive mutant (LA90) of RSV have been used to investigate possible heterologous interactions between the pp60v-src tyrosyl kinase and the epidermal growth factor (EGF) and bradykinin receptors. The LA90 pp60v-src exhibits a very rapid activation t1/2 (less than 5 min) of protein kinase activity on decreasing the temperature from 40 degrees C to 35 degrees C. This change in temperature was also found to induce a very rapid decrease in the affinity for 125I-EGF of receptors on the RSV-LA90-infected cells but not of those on control parental cells. However, no significant changes were detected in the binding of 3H-bradykinin to either cell line. Two separable processes control the desensitization of the EGF receptor by pp60v-src, both of which are independent of protein kinase C. The first is rapid and transient, while the second is sensitive to cycloheximide and persists long after inactivation of pp60v-src.
...
PMID:Specific desensitization of the epidermal growth factor receptor by pp60v-src. 255 Apr 86

The redistribution of protein kinase C (Ca2+/phospholipid-dependent protein kinase) from a cytosolic or a loosely associated membrane compartment to a more integral membrane compartment is stimulated by Ca2+ in vitro. This event is thought to be necessary for activation of the enzyme. To determine whether such a redistribution of protein kinase C occurs following hormonally stimulated increases in cytoplasmic Ca2+, we measured [3H]phorbol 12,13-dibutyrate ([3H]PDB) binding to protein kinase C in intact 1321N1 astrocytoma cells. The muscarinic agonist carbachol causes a 2-fold increase in [3H]PDB binding. This increase is transient, peaking at 1 min and returning toward control levels by 5 min. Scatchard analysis of [3H]PDB binding in the presence of carbachol reveals a 2-fold increase in the Bmax and no change in the KD compared to control values. This increase in Bmax likely represents a redistribution of protein kinase C to the membrane because [3H]PDB binding in intact cells is predominantly to membrane-associated enzyme. The Ca2+ ionophore ionomycin, and two other Ca2+-mobilizing hormones, bradykinin and histamine, mimic the effects of carbachol. Furthermore, when hormone-sensitive Ca2+ stores are depleted by prior agonist treatment, the carbachol-induced increases in intracellular [Ca2+] and [3H]PDB binding are completely blocked. Under these conditions, phosphoinositide hydrolysis and diacylglycerol (DAG) formation are not inhibited. We also examined the time course of DAG accumulation in response to carbachol. DAG is not yet significantly elevated when the increase in [3H]PDB binding is maximal. Furthermore, [3H]PDB binding has returned to control levels when DAG concentrations are maximally elevated. These data suggest that hormone-stimulated increases in cytoplasmic Ca2+ cause a marked and rapid redistribution of protein kinase C which precedes any significant increase in DAG. Our findings also demonstrate that [3H]PDB binding to intact cells may be a useful measure of the ability of Ca2+-mobilizing hormones to affect protein kinase C.
...
PMID:Increases in intracellular Ca2+ regulate the binding of [3H]phorbol 12,13-dibutyrate to intact 1321N1 astrocytoma cells. 278 92

We studied the action of bradykinin (BK) on ionic currents in fused pheochromocytoma PC12 cells under voltage-clamp in whole-cell mode, and on intracellular calcium using fura-2 BK induced the development of an outward current associated with an increase in intracellular calcium, followed by inhibition of an M-like current. The outward current was blocked by (+)-tubocurarine, and prevented when the calcium BAPTA or high concentrations of inositol 1,4,5-triphosphate were introduced into the cell, whereas the M-like current and its inhibition by BK remained unaffected. The protein kinase activator phorbol 12,13 dibutyrate partially reduced the M-current. M-current density did not substantially change after prolonged treatment with nerve growth factor.
...
PMID:Bradykinin inhibits a potassium M-like current in rat pheochromocytoma PC12 cells. 279 71

Exposure of A-431 cells to epidermal growth factor (EGF) results in a rapid enhancement (approximately 10-fold) of cytosolic serine protein kinase activity. The increase in serine kinase activity may be detected using a number of peptide and protein substrates. Enhancement of kinase activity occurs within 1 min of exposure of the cells to EGF and reaches a maximum in 5 min. Similar results were obtained with a variety of cell lines. We have partially purified the EGF-activated kinase from A-431 cells. It has an apparent molecular mass of approximately 100 kDa by gel filtration. One distinguishing property of the enzyme is its sensitivity to inhibition by micromolar quantities of polyarginine; polylysine has no effect. The EGF-activated kinase is unaffected by cyclic nucleotides, Ca2+/calmodulin, Ca2+/diolein/phosphatidylserine, or heparin. The enhancement of cytosolic serine kinase activity in A-431 cells appears to be an early event in cell "activation" by a number of biological response modifiers including EGF, bradykinin, 12-O-tetradecanoylphorbol-13-acetate, and histamine.
...
PMID:Activation of a cytosolic serine protein kinase by epidermal growth factor. 297 35

Growth-arrested human fibroblasts respond to mitogenic stimulation with a rapid, transient increase in cytoplasmic free Ca2+. This event may be crucial to the activation of Na/H exchange and subsequent DNA synthesis. Previous studies have implicated calmodulin (CaM) as a possible mediator of the effects of Ca2+ on these processes. here, we demonstrate that a specific CaM-dependent protein kinase (CaM-PK) system is rapidly activated in quiescent fibroblasts stimulated by a variety of mitogens. Cytoplasmic extracts of two human fibroblast cell types contained a major Ca2+-stimulated phosphoprotein of Mr 100,000 and pI 6.8 (Mr 100,000). This protein was shown by peptide mapping and immunological criteria to be identical to the prominent CaM-PK III substrate previously identified in a number of mammalian cells and tissues (Palfrey, H. C. (1983) FEBS Lett. 157, 183-190; Nairn, A.C., Bhagat, B., and Palfrey, H.C. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 7939-7943). Stimulation of 32P-labeled serum-deprived fibroblasts with serum, individual growth factors (bradykinin, vasopressin, and epidermal growth factor), or Ca2+ ionophores resulted in a rapid 2- to 10-fold increase in the phosphorylation of Mr 100,000 as determined by immunoprecipitation using polyclonal antibodies. With serum or individual growth factors, the effect peaked at 0.5-1 min then declined back to base line within 5 min. Time course studies showed that the phosphorylation state of Mr 100,000 closely paralleled but lagged slightly behind the Ca2+ transient (measured with fura-2). Thus, dephosphorylation of Mr 100,000 must follow shortly after Ca2+ levels begin to decline. The effects of serum, bradykinin, and vasopressin on both the rise in intracellular Ca2+ and the phosphorylation of Mr 100,000 were independent of external Ca2+, whereas the effects of epidermal growth factor and A23187 required external Ca2+. Phosphorylation of Mr 100,000 in intact cells took place on threonine residues, a major portion occurring in the same major phosphopeptide found in the protein labeled in vitro. These results show that mitogenic activation of human fibroblasts leads to the binding of Ca2+ to CaM and the subsequent activation of CaM-dependent processes.
...
PMID:Rapid activation of calmodulin-dependent protein kinase III in mitogen-stimulated human fibroblasts. Correlation with intracellular Ca2+ transients. 349 38

Cells of the T cell hybridoma 23A4 produce IgE-binding factors lacking N-linked oligosaccharides (unglycosylated form) when they are incubated with IgE alone. In the presence of glycosylation-enhancing factor (GEF) or bradykinin, however, the same cells produce IgE-binding factors with N-linked oligosaccharides (glycosylated form). Switching the cells from the formation of unglycosylated IgE-binding factors to the formation of glycosylated factors was accompanied by the release of both glycosylation-inhibiting factor (GIF) in its phosphorylated form, i.e., phosphorylated lipomodulin, and arachidonate from the cells. Analysis of the biochemical processes for the release of GIF from 23A4 cells showed that affinity-purified GEF or bradykinin induced transient phospholipid methylation and diacylglycerol (DAG) formation, and enhanced 45Ca uptake into the cells. Inhibitors of methyltransferases, i.e., 3-deaza-adenosine plus L-homocysteine thiolactone, inhibited not only phospholipid methylation but also DAG formation and GIF release. Exogenously added 1-oleoyl-2-acetyl glycerol, i.e., a DAG that is permeable to the plasma membrane, induced the release of GIF from the cells. It was also found that 12-O-tetradecanoyl-phorbol 13-acetate (TPA) switched 23A4 cells and normal lymphocytes to the selective formation of N-glycosylated IgE-binding factor, and induced the release of GIF from the cells. 32PO4-labeled lipomodulin was detected in the extract of 23A4 cells 3 to 5 min after the addition of GEF, bradykinin, or TPA. These results indicate that GEF and bradykinin induced the activation of methyltransferases and phospholipase C for the formation of DAG, which in turn activated Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) for the phosphorylation of lipomodulin. Because lipomodulin loses phospholipase inhibitory activity after phosphorylation, increased phospholipase A2 activity would be expressed by this process.
...
PMID:Modulation of the biologic activities of IgE-binding factors. VII. Biochemical mechanisms by which glycosylation-enhancing factor activates phospholipase in lymphocytes. 387 9

We have prepared a fluorescent conjugate of porcine calmodulin with 5-(dimethylamino)-1-naphthalene-sulfonyl chloride that is highly sensitive to both calcium binding and protein binding. We have used the fluorescence of this conjugate in addition to the intrinsic peptide fluorescence to show that adrenocorticotropic hormone (ACTH), beta-endorphin, glucagon, and substance P undergo calcium-dependent binding by calmodulin, with competition for common binding sites. The dissociation constants determined in the presence of 0.85 mM CaCl2 and 0.2 N KC1, pH 7.3 at 25 degrees C, range from 1.5 muM to 3.4 muM. The alpha-melanocyte-stimulating hormone, bombesin, and somatostatin also bind, with dissociation constants between 60 muM and 90 muM. Angiotensins I and III, bradykinin, neurotensin, physalaemin, substance P octapeptide, insulin, and Leu- and Met-enkephalin show little or no binding. Sequence comparisons show that the peptides that bind calmodulin well contain regions structurally similar to the recognition sequence for the cAMP-dependent protein kinase and to the sequences surrounding phosphorylated serine residues in several calmodulin binding proteins. This result suggests that modification of calmodulin binding sites in calmodulin-dependent proteins is one of the functions of protein kinase. Calcium has a dual role in peptide binding by calmodulin. The occupation of calcium binding sites having a pK approximately 4 results in a 2-fold increase in peptide binding affinity.
...
PMID:Binding of simple peptides, hormones, and neurotransmitters by calmodulin. 618 Jul 61

Using a rabbit anti-human prekallikrein antibody crossed immunoelectrophoresis (CIE) and Laurell rocket antigen determinations were done in plasma of subjects with Fletcher (prekallikrein, PKA), Fitzgerald (high molecular weight kininogen), Hageman (XII), and PTA (XI) deficiencies as well as in patients with activation of coagulation (intravascular coagulation syndromes). Abnormal CIE patterns were seen in the Fletcher and Fitzgerald deficient plasmas and also in some of the patients with intravascular coagulation. In vitro studies of plasma treated with thrombin, plasmin, and contact activating agents indicated that abnormal CIE patterns and increased PKA antigen levels were indicative of activation of the Hageman factor dependent pathway and not the result of plasma clotting by thrombin. In vivo activation of the Hageman factor dependent pathway frequently results in an abnormal CIE and a low PKA antigen level.
...
PMID:Immunoelectrophoretic studies of prekallikrein in human plasma. 691 63


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

---