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)

In patients who required volume expansion during extracorporeal circulation, the plasma bradykinin concentration was monitored simultaneously with the mean arterial pressure during infusion of either albumin solution or PPF. The PKA content of the PPF and the albumin solution was 29 and 3 U/L, respectively, measured spectrophotometrically. In six patients receiving 250 ml of PPF, the mean arterial pressure decreased 22% to 54% within 1.5 min after infusion, whereas the plasma bradykinin concentration, measured by radioimmunoassay, increased significantly (p less than 0.0005) during the first minute. In six patients receiving 250 ml of 4% albumin solution, no blood pressure changes were found, and the plasma bradykinin concentration rose only slightly. In vitro, linear correlation (r = 0.94, p less than 0.0005) was observed between the level of PKA of 26 different lots of PPF and the concentrations of bradykinin that were generated in Hageman factor-deficient plasma after incubation with PPF. It is concluded that the hypotensive reactions observed after PPF infusion during extracorporeal circulation are caused by the PKA-induced bradykinin generation.
 ...
PMID:Bradykinin-mediated hypotension after infusion of plasma-protein fraction. 698 Feb 51

In a rat model, the relationship between the activity of PKA in human PPFs, the changes in arterial BK concentration, and the changes in blood pressure on infusion of PPF was investigated. The rat was chosen as a model because it is reported to be one of the few animals sensitive to human PKA. However, hypotensive reactions after infusion of human PKA-containing PPF were observed only in the presence of a bradykinin-potentiating peptide (BPP9a). A correlation was found between the PKA content of the rapidly infused PPF, the BK generation in the rat, and the fall in arterial blood pressure. In control experiments, infusions of BK provoKed a similar fall in blood pressure at corresponding BK levels. After neutralization of the PKA activity in the PPF with C1-esterase inhibitor, neither a rise in BK level nor a fall in blood pressure was observed on infusion. We conclude therefore that the hypotensive reactions were caused by PKA-mediated generation of BK.
 ...
PMID:Hypotensive effects of plasma protein fraction. The relation between prekallikrein activator, bradykinin generation, and blood pressure in an animal model. 698 75

Prostaglandins enhance the sensitivity of sensory neurons to excitatory chemical agents such as bradykinin. The intracellular transduction cascades mediating this potentiation remain largely unknown. We have examined the role of cyclic AMP in the prostaglandin E2-induced potentiation of sensory neurons. Pretreatment with agents that elevate intracellular cyclic AMP levels enhances the number of action potentials elicited by bradykinin in a manner analogous to that of prostaglandin E2. The prostaglandin E2-induced potentiation of the number of bradykinin-elicited action potentials is blocked by either inhibition of adenylyl cyclase or protein kinase A. Therefore, our results suggest that prostaglandin E2 activates adenylyl cyclase to increase intracellular cyclic AMP, which in turn activates protein kinase A. Presumably activation of protein kinase A leads to increased levels of protein phosphorylation that then contribute to the enhancement of neuronal sensitivity to excitatory chemical agents.
 ...
PMID:Cyclic AMP mediates the prostaglandin E2-induced potentiation of bradykinin excitation in rat sensory neurons. 747 86

Nitric oxide is a signaling molecule involved in events crucial to neuronal cell function, such as neurotransmitter release, gene transcription, and neurotoxicity, i.e., a number of processes in which a key role appears to be played by increases in intracellular Ca2+ concentration. In the neurosecretory/neuronal cell line PC-12, we have investigated the role of nitric oxide in the modulation of Ca2+ release from intracellular stores elicited by activation of three different receptors coupled to phosphatidyl-inositol-4,5-bisphosphate hydrolysis, i.e., the purinergic P2U, muscarinic M3, and bradykinin B2 receptors. The results obtained show that nitric oxide donors have an inhibitory effect on agonist-evoked Ca2+ release. This effect is not due to nitric oxide-induced modifications of Ca2+ storage, because the total releasable Ca2+ pool, measured as the radioactivity released by thapsigargin and ionomycin in cells loaded at equilibrium with 45Ca2+, was unchanged. In contrast, nitric oxide donors decreased agonist-evoked inositol-1,4,5-trisphosphate generation and total inositol phosphate accumulation. Similarly, nitric oxide inhibited total inositol phosphate accumulation stimulated by either aluminium fluoride or Ca2+. All of these effects were mimicked by the cGMP analogue 8-bromo-cGMP. When cells were incubated with nitric oxide synthase inhibitors, the results observed were opposite those produced by nitric oxide donors. All of the effects of nitric oxide were abolished when cells were treated with the cGMP-dependent protein kinase I inhibitor KT5823. Furthermore, KT5823 mimicked the effects of nitric oxide synthase inhibitors. We conclude that nitric oxide and Ca2+ signaling pathways are interconnected in PC-12 cells. Modulation of inositol phosphate generation and Ca2+ release by nitric oxide appears to be exerted primarily at the level of phospholipase C functioning and to be mediated by the activation of cGMP-dependent protein kinase I.
 ...
PMID:Nitric oxide modulation of agonist-evoked intracellular Ca2+ release in neurosecretory PC-12 cells: inhibition of phospholipase C activity via cyclic GMP-dependent protein kinase I. 753 79

Regulation of phospholipases C (PLC) and arachidonic acid (AA) release by cAMP-dependent protein kinase (PKA) was investigated in MDCK-D1 cells. Bradykinin (BDK) was used to stimulate PLC and AA release, while arginine vasopressin (AVP), forskolin (FSK), isobutylmethylxanthine (IBMX) were used to increase cAMP levels and stimulate PKA. When cells were preincubated for 20 min with 10 microM FSK + 0.5 mM IBMX, and subsequently treated with 1 microM BDK or control medium for 40 min, the basal and BDK-stimulated PLC activity, measured as accumulated labelled inositol phosphate (InsP) after 40 min and inositol trisphosphate (InsP3) after 10 s, were significantly inhibited. In a parallel manner, FSK + IBMX also significantly decreased both basal and BDK-stimulated diacylglycerol (DAG) production. The basal and BDK-enhanced AA release into the media was also significantly inhibited by pretreatment with FSK + IBMX. In parallel experiments, H-89, a specific inhibitor of PKA, was preincubated for 60 min prior to addition of BDK and this resulted in a reversal of FSK+IBMX-induced inhibition of basal and BDK-stimulated PLC activity and AA release. An inhibitor of inositide-hydrolysing PLC, U73122, (1 microM) was also found to blunt BDK-stimulated PLC activity and BDK-enhanced AA release which indicated that stimulation of AA release by the nonapeptide was second to PLC activation. The ionophore, A23187, (10 microM) greatly stimulated AA release and to a much lesser extent, PLC activity. Its effect on AA release however was not blocked by inhibiting protein kinase C (PKC) with staurosporine (SSP) and consequently did not notably involve the PLC-PKC cascade. Activation of PKA with FSK + IBMX was found to significantly inhibit the enhancement of AA release by ionophore. With 12-tetradecanoyl-phorbol-13-acetate (TPA) also present there was a synergistic increase in the A23187-stimulated AA release and activation of PKA under such conditions inhibited AA release to a similar extent though the synergistic effect remained. The results strongly suggest a role for PKA in the regulation of PLC activity and AA release in MDCK-D1 cells. Control of AA release by PKA, is mediated both by mechanisms which involve blunting of PLC activity and mechanisms which are downstream from the PLC-PKC cascade.
 ...
PMID:Regulation of bradykinin-stimulated phospholipase C and arachidonic acid release by protein kinase A in MDCK-D1 cells. 754 85

Modification of chloride conductance by bradykinin in epithelial cells has been attributed to an activation of protein kinase A resulting from adenylcyclase stimulation by arachidonic acid cyclooxygenase products. The results presented here compare tracheal epithelial cell lines from one control and two cystic fibrosis patients which were immortalized by transfection with the SV40 large T oncogene. The three cell lines presented the same arachidonic acid content, turnover and mobilisation under basal conditions. Bradykinin stimulated the release of arachidonic acid and the synthesis of cyclooxygenase derivatives (mainly PGE2). The cell line from the cystic fibrosis patient bearing a phenylalanine 508 deletion, which is the major form of the disease, showed a higher bradykinin-induced arachidonic acid release than either control cells or cells from a patient presenting a minor form of the disease. This higher sensitivity suggests a dysregulation of phospholipase A2 stimulation in cystic fibrosis cells and was confirmed on non-immortalized tracheal epithelial cells in primary culture and on skin fibroblasts from patients bearing the same mutation. This defect is associated with a potentiation of cholera toxin pretreatment on cAMP content of delta F508 cell line. The impaired control of arachidonic acid release cannot be attributed to an increased number of bradykinin binding sites, since this increase was similar in the two cystic fibrosis cell lines.
 ...
PMID:Increase of bradykinin-stimulated arachidonic acid release in a delta F508 cystic fibrosis epithelial cell line. 768

Regulations of the increase in intracellular Ca2+ concentration ([Ca2+]i) and inositol 1,4,5-trisphosphate (IP3) production by increasing intracellular cyclic AMP (cAMP) levels or activating protein kinase C (PKC) were studied in rat frontocortical cultured neurons. Amitriptyline (AMI; 1 mM), a tricyclic antidepressant, and bradykinin (BK; 1 microM) stimulated IP3 production and caused transient [Ca2+]i increases. Pretreatment with forskolin (100 microM, 15 min) decreased the AMI- and BK-induced [Ca2+]i increases by 33 and 48%, respectively. However, this treatment had no effect on the AMI- and BK-induced IP3 productions. Dibutyryl-cAMP (2 mM, 15 min) also decreased the AMI- and BK-induced [Ca2+]i increases by 23 and 47%, respectively. H-8 (30 microM), an inhibitor of protein kinase A (PKA), attenuated the ability of forskolin to inhibit the AMI- and BK-induced [Ca2+]i increases, suggesting that the activation of cAMP/PKA was involved in these inhibitory effects of forskolin. On the other hand, forskolin treatment had no effect on 20 mM caffeine-, 10 microM glutamate-, or 50 mM K(+)-induced [Ca2+]i increases. Pretreatment with phorbol 12-myristate 13-acetate (PMA; 100 nM, 90 min) decreased both the AMI-induced [Ca2+]i increases and the IP3 production by 31 and 25%, respectively. H-7 (200 microM), an inhibitor of PKC, inhibited the ability of PMA to attenuate the [Ca2+]i increases. PMA also inhibited the BK-induced IP3 production and the [Ca2+]i increases.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Forskolin and phorbol myristate acetate inhibit intracellular Ca2+ mobilization induced by amitriptyline and bradykinin in rat frontocortical neurons. 769 65

We describe here the isolation of a novel non-collagenous protein from the acid demineralization extract of bovine cortical bone. This 24-kDa protein is multiply phosphorylated at serine residues in Ser-X-Glu/Ser(P) sequences, a recognition motif for phosphorylation by the secretory pathway protein kinase, and we have termed this protein secreted phosphoprotein 24 (spp24). The cDNA structure of spp24 was determined by sequencing cDNA fragments obtained by reverse transcription-polymerase chain reaction, 3'-rapid amplification of cDNA ends, and screening a lambda gt11 cDNA library. This cDNA sequence predicts a 200-residue initial translation product which consists of a 20-residue signal sequence and the 180-residue mature spp24. Northern blot analysis using the spp24 cDNA showed that spp24 mRNA is in liver and bone but not in heart, lung, kidney, or spleen. A search of existing protein sequences revealed that the N-terminal 107 residues of mature spp24 are related in sequence to the cystatin family of thiol protease inhibitors, which suggests that spp24 could function to modulate the thiol protease activities that are known to be involved in bone turnover. Several of the proteins in the cystatin family that are most closely related to spp24 are not only thiol protease inhibitors but are also precursors to peptides with potent biological activity, peptides such as bradykinin and the neutrophil antibiotic peptides. It is therefore possible that the intact form of spp24 found in bone could also be a precursor to a biologically active peptide, a peptide which could coordinate an aspect of bone turnover.
 ...
PMID:Isolation and molecular cloning of a novel bone phosphoprotein related in sequence to the cystatin family of thiol protease inhibitors. 781 6

To study signaling pathways regulated by alpha s and alpha i1 in renal epithelial cells, we expressed mutant, activated forms of alpha s and alpha i1 in a continuous proximal tubule cell line (MCT cells). alpha sQ227L increased cAMP production, and alpha ilQ204L reduced forskolin-sensitive cAMP production. alpha ilQ204L increased and alpha sQ227L decreased bradykinin-induced Ca influx across the cell membrane, but neither mutant affected bradykinin-stimulated intracellular Ca release or basal Ca influx. Bradykinin-stimulated Ca influx was reduced by dibutyryl cAMP, isoproterenol, and forskolin. Expression of a mutant regulatory type I subunit for cAMP-dependent protein kinase with reduced affinity for cAMP and treatment with KT-5720, a specific cAMP-dependent protein kinase inhibitor, enhanced Ca influx to a degree similar to that in cells expressing alpha ilQ204L. Bradykinin-stimulated c-fos mRNA expression is partially dependent on extracellular Ca. alpha sQ227L reduced and alpha ilQ204L enhanced bradykinin-stimulated c-fos expression. Consequently, in bradykinin-stimulated cells, the adenylyl cyclase system regulates Ca influx through cAMP-dependent protein kinase, but not intracellular Ca release. Furthermore, the Ca influx mechanism acts as an integrator of two signaling pathways such that Ca-dependent signals are damped by activators of adenylyl cyclase and enhanced by inhibitors of adenylyl cyclase.
 ...
PMID:Regulation of hormone-sensitive calcium influx by the adenylyl cyclase system in renal epithelial cells. 804 Feb 74

Intact bovine adrenal medullary chromaffin cells were preincubated with 32PO4, and the multiple-site phosphorylation of tyrosine hydroxylase (TH) was studied. Up to eight 32P-labeled peptides were produced by tryptic hydrolysis of TH; however, all of the tryptic phosphopeptides were derived from four phosphorylation sites--Ser8, Ser19, Ser31 and Ser40. In situ regulation of 32P incorporation into the latter three sites was demonstrated with a diverse set of pharmacological agents. 32P incorporation into Ser19 was preferentially increased by brief exposures to depolarizing secretagogues. Longer treatments also increased Ser31 and Ser40 phosphorylation. Nicotine, muscarine and vasoactive intestinal polypeptide--reflecting cholinergic and non-cholinergic components of sympatho-adrenal transmission--each produced different patterns of multiple-site phosphorylation of TH. Nicotine, bradykinin and histamine increased 32P incorporation at each of the three sites whereas muscarine, angiotensin II, endothelin III, prostaglandin E1, GABA and ATP selectively increased Ser31 phosphorylation. Nerve growth factor did not influence TH phosphorylation in chromaffin cells from adult adrenal glands but selectively increased Ser31 phosphorylation in chromaffin cells isolated from calf adrenal glands. 32P incorporation into Ser40 was selectively increased by forskolin and other cAMP-acting agents whereas vasoactive intestinal polypeptide increased Ser31 and Ser40 phosphorylation. Thus, the phosphorylation of TH in bovine chromaffin cells appears to be regulated at three sites by three separate intracellular signaling pathways--Ser19 via Ca2+/calmodulin-dependent protein kinase II; Ser31 via ERK (MAP2 kinases); and Ser40 via cAMP-dependent protein kinase. These signaling pathways, as well as the extracellular signals that were effective in stimulating them, are similar to those previously described for TH in rat pheochromocytoma cells. However, several of the pharmacological agents produced different patterns of multiple-site TH phosphorylation in the bovine chromaffin cells. These differences between tissues could be accounted for by differences in the coupling/access between the extracellular signal transduction systems and the intracellular signaling pathways as opposed to differences in the intracellular signaling pathways per se.
 ...
PMID:Multiple signaling pathways in bovine chromaffin cells regulate tyrosine hydroxylase phosphorylation at Ser19, Ser31, and Ser40. 809 28


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