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)

Previous studies using phorbol esters and cell-free preparations suggest that protein kinase C (PKC) may regulate Cl- secretion and apical membrane Cl- channels in airway epithelium. To determine whether PKC may be involved in receptor-mediated control of secretion, we measured the mass of diacylglycerol (DAG) generated by two Cl- secretagogues, isoproterenol and bradykinin. Bradykinin increased cellular DAG at concentrations similar to those that increase inositol phosphates, suggesting that bradykinin stimulates phosphatidylinositol hydrolysis, as observed in other systems. Isoproterenol also increased cellular DAG at concentrations similar to those that stimulate adenosine 3',5'-cyclic monophosphate (cAMP) accumulation. The beta-adrenergic receptor antagonist, nadolol, blocked and cell-permanent analogues of cAMP mimicked the effect of isoproterenol. However, isoproterenol does not stimulate phosphatidylinositol turnover. Simultaneous addition of maximal concentrations of isoproterenol and bradykinin produced additive increases in DAG. To test the possibility that the isoproterenol-induced increase in DAG came from phosphatidylcholine turnover, we measured the release of water-soluble choline metabolites and the incorporation of choline into cellular lipids. Although phorbol ester and bradykinin stimulated phosphatidylcholine turnover, isoproterenol did not. These results suggest that isoproterenol and bradykinin generate DAG from the following different lipid sources: bradykinin stimulates phosphatidylinositol hydrolysis to produce DAG; isoproterenol stimulates an increase in DAG from unknown sources. The data suggest that simultaneous activation of cAMP-dependent protein kinase and PKC may occur during receptor-mediated stimulation of Cl- secretion.
...
PMID:Isoproterenol, cAMP, and bradykinin stimulate diacylglycerol production in airway epithelium. 216 9

The whole-cell voltage-clamp technique was employed to study the beta-adrenergic modulation of voltage-gated K+ currents in CD8+ human peripheral blood lymphocytes. The beta-receptor agonist, isoproterenol, decreased the peak current amplitude and increased the rate of inactivation of the delayed rectifier K+ current. In addition, isoproterenol decreased the voltage dependence of steady-state inactivation and shifted the steady-state inactivation curve to the left. Isoproterenol, on the other hand, had no significant effect on the steady-state parameters of current activation. The isoproterenol-induced decrease in peak current amplitude was inhibited by the beta-blocker propranolol. Bath application of dibutyryl cAMP (1 mM) mimicked the effects of isoproterenol on both K+ current amplitude and time course of inactivation. Furthermore, the reduction in the peak current amplitude in response to isoproterenol was attenuated when PKI5-24 (2-5 microM), a synthetic peptide inhibitor of cAMP-dependent protein kinase, was present in the pipette solution. The increase in the rate of inactivation of the K+ currents in response to isoproterenol was mimicked by the internal application of GTP-gamma-S (300 microM) and by exposure of the cell to cholera toxin (1 microgram/ml), suggesting the involvement of a G protein. These results demonstrate that the voltage-dependent K+ conductance in T lymphocytes can be modulated by beta-adrenergic stimulation. The effects of beta-agonists, i.e., isoproterenol, appear to be receptor mediated and could involve cAMP-dependent protein kinase as well as G proteins. Since inhibition of the delayed rectifier K+ current has been found to decrease the proliferative response in T lymphocytes, the beta-adrenergic modulation of K+ current may well serve as a feedback control mechanism limiting the extent of cellular proliferation.
...
PMID:Beta-adrenergic modulation of K+ current in human T lymphocytes. 217 47

Ileal brush border membranes contain an endogenous Ca2+/calmodulin (CaM)-dependent protein kinase activity that modulates the activity of the apical membrane Na+/H+ exchanger. To further characterize this kinase, synapsin I, a substrate for Ca2+/CaM-dependent protein kinases, was added to preparations of ileal brush border membranes. In the presence of Ca2+/CaM, synapsin I was phosphorylated. Phosphopeptide mapping demonstrated that the addition of Ca2+/CaM to brush border membranes stimulated the phosphorylation of sites in synapsin I specific for Ca2+/CaM-dependent protein kinase II. Immunoblots containing brush border and microvillus membrane proteins were probed with an antibody that recognizes the 50-kDa subunit of rat brain Ca2+/CaM-dependent protein kinase II. This antibody labeled major and minor species of 50 and 53 kDa, respectively, with more labeling of the brush border than the microvillus membranes. Right-side-out ileal villus cell brush border vesicles were prepared containing CaM, ATP, and 350 nM free Ca2+. Na+/H+ exchange was inhibited by the presence of Ca2+/CaM/ATP within the vesicles. A 21-amino acid peptide inhibitor of CaM kinase II was enclosed within some vesicle preparations by freeze-thaw. The effect on Na+/H+ exchange of Ca2+/CaM/ATP was partially reversed by the inhibitor peptide. These studies demonstrate the presence of Ca2+/CaM-dependent protein kinase II in rabbit ileal villus cell brush border membranes. Based on the effect of a specific inhibitor peptide of Ca2+/CaM kinase II, it is concluded that this kinase inhibits brush border Na+/H+ exchange, which participates in the regulation of ileal Na+ absorption.
...
PMID:Rabbit ileal villus cell brush border Na+/H+ exchange is regulated by Ca2+/calmodulin-dependent protein kinase II, a brush border membrane protein. 217 71

Phosphorylation of the insulin-regulatable glucose transporter (IRGT) is increased by incubating rat adipocytes with isoproterenol or by incubating microsomal membranes with cAMP-dependent protein kinase. To attempt to locate the sites of phosphorylation, the IRGT (apparent Mr = 46,000) was immunoprecipitated from 32P-labeled adipocytes and cleaved with CNBr or trypsin. Essentially all of the 32P could be recovered in a single CNBr fragment, denoted CB-T (Mr = 8,000), which bound a polyclonal antibody (R820) against a peptide having the sequence of the last 12 amino acids in the COOH terminus of the IRGT. 32P-Labeling of the IRGT was also confined to CB-T when membranes were incubated with [gamma-32P]ATP and cAMP-dependent protein kinase. Isoproterenol increased phosphorylation of CB-T, but insulin was without effect. To resolve phosphorylation sites further, IRGT from 32P-labeled cells was subjected to exhaustive proteolysis with trypsin. Samples were applied to a C-18 column, and 32P-labeled fragments were resolved into three peak fractions by elution with an increasing gradient of acetonitrile. [32P]Phosphoserine was the only phosphoamino acid detected in any of the peaks. Peak III contained approximately 80% of the 32P and was increased by isoproterenol. Almost all of the 32P introduced by cAMP-dependent protein kinase in vitro eluted in Peak III. In all cases, the 32P-labeled species in Peak III were quantitatively immunoprecipitated by R820. Digesting the peptide(s) in Peak III with V8 protease generated a single peak of 32P which eluted at lower acetonitrile than Peak III and contained 32P-labeled species that did not interact with R820. Automated Edman degradation indicated that the serine residue in Peak III phosphorylated by cAMP-dependent protein kinase was the 3rd or 4th residue from the NH2 terminus of the peptide. These findings indicate that phosphorylation of the IRGT is restricted to the presumed intracellular domain at the COOH terminus and that Ser488 is a major site phosphorylated both by cAMP-dependent protein kinase in vitro and in response to isoproterenol in vivo.
...
PMID:Phosphorylation of the glucose transporter in rat adipocytes. Identification of the intracellular domain at the carboxyl terminus as a target for phosphorylation in intact-cells and in vitro. 240 83

The esophagus of Rana catesbeiana yielded 20-40 X 10(6) peptic cells that were greater than 80% pure by immunostaining, greater than 90% viable, and had low basal pepsinogen and lactic dehydrogenase (LDH) release. Cellular responses to agents that bypass receptors and act directly on cell messenger systems have been compared with receptor-mediated activation. Pepsinogen secretion was stimulated dose dependently by A23187, the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), and forskolin. The combination of any two or all three agents at optimum effective concentrations stimulated secretion to more than double the output of the sum of the individual responses. Incubation in Ca2+-free media reduced responses to A23187 and TPA but not forskolin. Ca2+ deprivation eliminated the synergism of messenger combinations. Secretory responses to combinations of the agonists bethanechol or bombesin with either A23187 or TPA were additive and were synergistic with forskolin. Isoproterenol plus bethanechol or bombesin produced synergistic responses that were significantly smaller than combinations of their putative messengers. The synergistic response to isoproterenol and bethanechol was dependent on extracellular Ca2+. These data suggest that although Ca2+ may function in peptic cells to stimulate secretion directly, it may also act as a gain control for synergistic interaction between other messenger pathways (protein kinase a and c).
...
PMID:Synergism between cellular messengers and agonist combinations in pepsinogen secretion. 244 14

The molecular mechanisms of myelin formation/reformation in the central nervous system are unknown. In previous work we have demonstrated that mature oligodendrocytes (OLG) respond to a signal(s), elicited by their adhesion to a substratum, by turning on a myelinogenic metabolism. Events occurring within 24 hr of adhesion include generation of diacylglycerol, activation of protein kinase C, phosphorylation of myelin basic protein, and enhanced synthesis of myelin lipids and proteins. To elucidate the mechanism(s) of signal transduction, we have investigated whether OLG-substratum interaction influences the level of basal cAMP and the expression of receptors coupled to adenylate cyclase. By using ovine brain OLG we have found that adhesion to a polylysine-coated surface for 24 hr increased the basal level of cAMP 2-fold and altered the expression (assessed by cAMP production) of receptors coupled to adenylate cyclase. Isoproterenol (beta-adrenergic agonist) augmented cAMP from 4 to 26 pmol/mg of protein in adhering OLG but had no such effect in nonattached OLG. Adhesion of OLG was accompanied by rapid synthesis of ethanolamine plasmalogen, a class of lipids believed to be associated with beta-adrenergic receptors. Nonattached OLG responded to prostaglandin E1 with only a 3-fold stimulation in their cAMP content; in attached OLG, 6-fold stimulation was observed. In contrast, vasoactive intestinal polypeptide elicited a 3-fold increase in cAMP in nonattached OLG but, following 24 hr of attachment, OLG did not respond to vasoactive intestinal polypeptide. The increase of cellular cAMP levels was accompanied by a 2.5-fold gain in protein kinase A. OLG-substratum adhesion resulted also in phosphorylation of the OLG/myelin protein, 2',3'-cyclic nucleotide 2'-phosphodiesterase, which proved to be a substrate for cAMP and phospholipid-, Ca2+-dependent protein kinases. These findings, in conjunction with our earlier work, implicate cAMP and diacylglycerol in signaling myelinogenesis; they suggest that phosphorylation/dephosphorylation of myelin basic protein and 2',3'-cyclic nucleotide 2'-phosphodiesterase may be key processes in the cascade of events that are initiated by adhesion of OLG to a polylysine surface (possibly acting as a surrogate for axons) and culminate in the reformation of myelin.
...
PMID:Oligodendrocyte substratum adhesion modulates expression of adenylate cyclase-linked receptors. 244 85

beta-Adrenergic stimulation of ventricular heart cells results in the enhancement of two important ion currents that regulate the plateau phase of the action potential: the delayed rectifier potassium channel current (IK) and L-type calcium channel current (ICa). The temperature dependence of beta-adrenergic modulation of these two currents was examined in patch-clamped guinea pig ventricular myocytes at various steps in the beta-receptor/cyclic AMP-dependent protein kinase pathway. External applications of isoproterenol and forskolin were used to activate the beta-receptor and the enzyme adenylate cyclase, respectively. Internal dialysis of cyclic 3',5'-adenosine monophosphate (cAMP) or the catalytic subunit of cAMP-dependent protein kinase (CS), as well as the external addition of 8-chlorphenylthio cAMP (CPT-cAMP) was applied to increase intracellular levels of cAMP and CS. Isoproterenol-mediated increases in IK, but not ICa, were found to be very temperature dependent over the range of 20-37 degrees C. At room temperature (20-22 degrees C) isoproterenol produced a large (threefold) enhancement of ICa but had no effect on IK. In contrast, at warmer temperatures (30-37 degrees C) both currents increased in the presence of this agonist and the kinetics of IK were slowed at -30 mV. A similar temperature sensitivity also existed after exposure to forskolin, CPT-cAMP, cAMP, and CS, suggesting that this temperature sensitivity of IK may arise at the channel protein level. Modulation of IK during each of these interventions was accompanied by a slowing in IK kinetics. Thus, regulation of cardiac potassium channels but not calcium channels involves a temperature-dependent step that occurs after activation of the catalytic subunit of cAMP-dependent protein kinase.
...
PMID:Beta-adrenergic modulation of cardiac ion channels. Differential temperature sensitivity of potassium and calcium currents. 247 62

Expression of tissue plasminogen activator (tPA) gene is stimulated by gonadotropins in granulosa cells. Because adrenergic agents interact with specific granulosa cell receptors to increase progesterone biosynthesis, the effects of these pounds on tPA activity and mRNA levels were also investigated. Cells obtained from immature estrogen-treated rats were initially cultured with FSH or medium alone for 2 days. They were then reincubated with various adrenergic agents before measurement of medium tPA activity using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by a fibrin overlay technique. In addition, cellular RNA was extracted, and tPA mRNA levels were analyzed using a specific rat cRNA probe. Isoproterenol, a beta-adrenergic agonist, stimulated the secretion of tPA activity in a dose-dependent manner, with FSH-pretreated cells secreting higher levels of the enzyme than cells without FSH priming. Northern blot hybridization of total RNA showed the accumulation of a 22S species tPA message in cells treated with isoproterenol, suggesting increased expression of the tPA gene. Furthermore, slot blot hybridization of RNA from these cells indicated a time-dependent increase in tPA mRNA, with maximal induction between 1-3 h of incubation. A selective beta 2-adrenergic agonist, terbutaline, but not the beta 1-agonist dobutamine, stimulated tPA activity. Also, the stimulatory effect of isoproterenol was blocked by a beta 2-antagonist (ICI-118,551) but not by a beta 1-antagonist (practolol), suggesting the involvement of a beta 2-receptor. Like FSH and LH, isoproterenol increased extra- and intracellular cAMP levels. Cotreatment of a saturating dose of isoproterenol with FSH or LH did not further stimulate tPA activity. Similar to that in cells treated with FSH, inhibition of protein synthesis by cycloheximide resulted in the superinduction of tPA mRNA in isoproterenol-treated cells. Thus, activation of beta 2-adrenergic receptors in granulosa cells induces tPA mRNA and activity, presumably through the protein kinase-A pathway shared by gonadotropins. Adrenergic neurotransmitters may be potential intraovarian regulators of this important protease.
...
PMID:Beta-adrenergic agents stimulate tissue plasminogen activator activity and messenger ribonucleic acid levels in cultured rat granulosa cells. 247 32

The possible involvement of three different second-messenger systems, namely cyclic AMP/protein kinase (PK)-A, cyclic GMP/PK-G, and diacylglycerol (DG)/PK-C systems, in the perivascular nerve terminals of guinea pig mesenteric artery was examined by intracellular microelectrode recording. Excitatory junction potentials (EJPs) were evoked by perivascular nerve stimulation. Isoproterenol (0.1 microM) enhanced the EJP amplitude without modifying the passive membrane properties of the vascular smooth muscle (VSM) cells. The facilitatory effect of isoproterenol on EJP amplitude was completely abolished by beta-adrenergic blockade (0.3 microM propranolol). Forskolin (activator of adenylate cyclase) also augmented the EJP amplitude in a concentration-dependent manner (EC50 congruent to 10 microM), without affecting the passive membrane properties of the VSM cells. In addition, forskolin (1-10 mM) markedly potentiated the isoproterenol-induced stimulation of EJP amplitude (EC50 congruent to 2 microM). A permeant analogue of cyclic AMP, 8-bromo-cyclic AMP (0.1 and 1 mM), enhanced the EJP amplitude, thus mimicking the effects of isoproterenol and forskolin. 8-Bromo-cyclic AMP had no effect on the resting potential or current-voltage relationship of the VSM cells, thus suggesting that the membrane properties of the VSM cells were not altered. 8-Bromo-cyclic GMP (1 mM) also augmented the EJP amplitude, but its facilitatory effect was weaker than that of 8-bromo-cyclic AMP. 8-Bromo-cyclic GMP hyperpolarized the VSM membrane by 4 mV and decreased the input resistance, presumably due to an increase in K+ conductance. Phorbol-12-myristate-13-acetate (PMA, 30-300 nM), a direct activator of PK-C, significantly enhanced the EJP amplitude after 40 min in a concentration-dependent manner, without affecting the resting potential of the VSM cells. From these results, we suggest that cyclic AMP/PK-A, cyclic GMP/PK-G, and DG/PK-C systems might be involved in regulation of the release of neurotransmitter in the perivascular nerve terminals. However, the possibility of some action on the postsynaptic VSM cell cannot be excluded.
...
PMID:Cyclic nucleotide regulation of neurotransmission in guinea pig mesenteric artery. 248 77

The time-courses of isoproterenol activation of rat adipocyte particulate low Km cAMP phosphodiesterase (PDE) activity, cAMP-dependent protein kinase (A-kinase), and glycerol production were measured in the presence and absence of insulin. Isoproterenol (100 nM) alone rapidly activated A-kinase 8- to 10-fold and increased particulate cAMP PDE by approximately 100%. A-kinase and PDE activity remained relatively constant for at least 25 to 30 min. Kact values for isoproterenol activation of PDE and lipolysis were similar. In comparison with isoproterenol, insulin (0.1-0.3 nM) alone increased particulate cAMP PDE at a slower rate and to a lesser extent (by approximately 50% within 12 to 16 min) and without any change in A-kinase. With insulin plus isoproterenol there was a rapid, transient, and synergistic activation of particulate cAMP PDE, which temporally correlated with a decrease in A-kinase and reduction in lipolysis. These and other data suggest the following: 1) there is a close concentration-dependent and temporal relationship in isoproterenol activation of adenylate cyclase, of A-kinase, and of particulate cAMP PDE; 2) isoproterenol and insulin activate particulate cAMP PDE by two distinct mechanisms; 3) the temporal changes in PDE and A-kinase in the presence of insulin and isoproterenol suggest that insulin activation of the PDE does not require, but may be enhanced by, elevated cAMP and is important in the antilipolytic action of insulin.
...
PMID:Role of hormone-sensitive low Km cAMP phosphodiesterase in regulation of cAMP-dependent protein kinase and lipolysis in rat adipocytes. 253 13


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

---