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)

Studies in the past several years have provided direct evidence that protein phosphorylation is involved in the regulation of neuronal function. Electrophysiological experiments have demonstrated that three distinct classes of protein kinases, i.e., cyclic AMP-dependent protein kinase, protein kinase C, and CaM kinase II, modulate physiological processes in neurons. Cyclic AMP-dependent protein kinase and kinase C have been shown to modify potassium and calcium channels, and CaM kinase II has been shown to enhance neurotransmitter release. A large number of substrates for these protein kinases have been found in neurons. In some cases (e.g., tyrosine hydroxylase, acetylcholine receptor, sodium channel) these proteins have a known function, whereas most of these proteins (e.g., synapsin I) had no known function when they were first identified as phosphoproteins. In the case of synapsin I, evidence now suggests that it regulates neurotransmitter release. These studies of synapsin I suggest that the characterization of previously unknown neuronal phosphoproteins will lead to the elucidation of previously unknown regulatory processes in neurons.
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PMID:Protein phosphorylation and neuronal function. 258 86

It was found that serotonin relaxed desensitization and decreased acetylcholine-induced potassium current. Effects of serotonin were connected with serotonin-activated adenylate cyclase, adenosine 3':5'-cyclic monophosphate (cAMP) and phosphorylation of muscarinic receptor proteins by cAMP-dependent protein kinase.
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PMID:[Serotonin modulation of the muscarinic cholinoreceptor status of the neurons in the mollusk Planorbarius corneus]. 260 68

Requirements for the activation of Cl- conductance have been investigated in pig jejunal brush border vesicles. The stability of ATP as a substrate for protein kinase activity, the stability of the phosphoprotein product of protein kinase action, and the choice of buffer system used for vesicle preparation were studied as variables which affected the outcome of in vitro activation attempts. Arsenate was selected as the most effective agent in protecting ATP from hydrolysis by the phosphatase activity in this vesicle system. Brush border vesicle protein appeared to prevent the accumulation of phosphoprotein in a cAMP-dependent protein kinase reaction, and vesicle protein only had phosphate acceptor activity when KF was added as a presumptive inhibitor of phosphoprotein phosphatase. A Cl- conductance response to a potassium gradient and valinomycin was present in vesicles prepared in buffers containing tetramethylammonium. Cl- conductance activity was not increased in this system by the addition of ATP, dibutyryl cyclic AMP, and cyclic AMP-dependent protein kinase. There was no Cl conductance response to a potassium gradient in vesicles buffered with imidazolium-acetate. Incorporation of ATP, AsO4(3-), and F- into these nonconductive vesicles by homogenization, followed by addition of dibutyryl cAMP, produced substantial conductance activity. Maximal activation of Cl- conductance was obtained with vesicles prepared in imidazolium-acetate buffering, using precautions to stabilize ATP and phosphoprotein prior to conductance measurements.
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PMID:Activation of chloride conductance in pig jejunal brush border vesicles. 271 42

ADH, acting through cAMP, increases the potassium conductance of apical membranes of mouse medullary thick ascending limbs of Henle. The present studies tested whether exposure of renal medullary apical membranes in vitro to the catalytic subunit of cAMP-dependent protein kinase resulted in an increase in potassium conductance. Apical membrane vesicles prepared from rabbit outer renal medulla demonstrated bumetanide- and chloride-sensitive 22Na+ uptake and barium-sensitive, voltage-dependent 86Rb+ influx. When vesicles were loaded with purified catalytic subunit of cAMP-dependent protein kinase (150 mU/ml), 1 mM ATP, and 50 mM KCl, the barium-sensitive 86Rb+ influx increased from 361 +/- 138 to 528 +/- 120 pM/mg prot.30 sec (P less than 0.01). This increase was inhibited completely when heat-stable protein kinase inhibitor (1 microgram/ml) was also present in the vesicle solutions. The stimulation of 86Rb+ uptake by protein kinase required ATP rather than ADP. It also required opening of the vesicles by hypotonic shock, presumably to allow the kinase free access to the cytoplasmic face of the membranes. We conclude that cAMP-dependent protein kinase-mediated phosphorylation of apical membranes from the renal medulla increases the potassium conductance of these membranes. This mechanism may account for the ADH-mediated increase in potassium conductance in the mouse mTALH.
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PMID:Activation of K+ channels in renal medullary vesicles by cAMP-dependent protein kinase. 276 36

This study describes various elements of the mechanism controlling norepinephrine (NE)-mediated release of serotonin (5HT) from rat pineal glands. After radiolabelling the endogenous pool of pineal 5HT with 3H-5HT, individual pineal glands were exposed to depolarizing buffers or those containing NE. Although 3H-5HT was not released by 50mM potassium, efflux of the indoleamine was increased by NE. Alpha-adrenergic receptors mediate the effects of NE as indicated by the fact that phenylephrine but not isoproterenol, a beta receptor agonist, also enhanced 3H-5HT release. This hypothesis is supported further by the fact that prazosin and phentolamine (alpha-antagonists) but not sotolal (beta-antagonist), inhibited the stimulatory effects of NE on 5HT release. In order to determine the intracellular second messenger involved in the 5HT release process, pineals were incubated with 8-bromo cAMP or the phorbol ester, PMA. PMA simulated the effects of NE and phenylephrine on 3H-5HT efflux, while cAMP had no effect. Furthermore, calcium-, phospholipid-dependent protein kinase activities in pineal homogenates were responsive to NE. These findings suggest that 5HT secretion from rat pinealocytes occurs rapidly in response to NE signals that act through alpha-adrenergic receptors in concert with phospholipid dependent protein kinase(s). These molecular processes are different from those involved in melatonin metabolism and may represent a general mechanism for regulating 5HT release in the brain.
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PMID:Molecular mechanisms controlling norepinephrine-mediated release of serotonin from rat pineal glands. 282 82

The effect of the activators of protein kinase A (dibutyryl-cAMP) and protein kinase C (beta-phorbolic ether), as well as cell compression, on the rate of 22Na and 86Rb, a radioactive potassium analogue, incorporation by human and rat erythrocytes was investigated. Protein kinase A and protein kinase C activation was accompanied by the activation of Na+, K+-ATP-ase in human and rat erythrocytes as well as increased Na+, K+ cotransport rate in rat erythrocytes. Human erythrocytes responded to protein kinase C activation by a 2 or 3-fold increase in Na+/Na+-antitransport rate, and both human and rat erythrocytes exhibited a manifold increase in the Na+/H+ metabolism rate. Cell compression depressed Na+, K+-ATP-ase activity and increased the rates of Na+/H+ metabolism and the frusemide-inhibited component of potassium transport, the latter two effects being particularly obvious in rat erythrocytes. It is suggested that protein kinase C activation and/or erythrocyte compression may be a direct cause of increased plasmatic membrane permeability for univalent cations in primary hypertension.
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PMID:[Univalent cation transport in human and rat erythrocytes: its regulation by protein kinase activators and compression]. 283 4

After the addition of valinomycin into the incubation medium, the potassium content of rat erythrocytes rapidly decreases. The rate-limiting step of this reaction is a unidirectional efflux of anions through band 3 protein. The rate of this efflux in erythrocytes of spontaneously hypertensive rats (SHR) of the Wistar-Kyoto strain, is not altered. The loss of KCl by rat erythrocytes is accompanied by a decrease in intracellular water, cell shrinking and activation of Na+-H+i exchange. The rate of Na+-H+ exchange in the erythrocytes of SHR in the pre-hypertensive stage (4 weeks old) was decreased by 30%. There were no differences between 14-week-old and 28-week-old SHR and normotensive Wistar-Kyoto (WKY) rats. The half-maximal increase of the valinomycin-induced Na+-H+ exchange in erythrocytes of 14-week-old WKY and SHR was observed at KCl concentrations in the incubation medium of 25 and 40 mmol, respectively. The addition of activators of protein kinase A (dibutyryl-cAMP) or protein kinase C (beta-phorbol ester) resulted in an increase in the maximal rate of Na+-H+ exchange, and did not modify its dependence on K+o concentration. In all groups of SHR, the rate of valinomycin-induced H+ efflux from erythrocytes in the sodium-free medium was 1.5-2.5-fold higher than in age-matched WKY. Under these conditions (addition of valinomycin and inhibition of Na+-H+ exchange), haemoglobin release from erythrocytes of SHR, treated with hypotonic solution, was significantly decreased. We conclude that these differences are due to the alteration of the skeleton protein organization in the erythrocyte membranes of SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transport of sodium and protons and hypotonic haemolysis in the valinomycin-treated erythrocytes of rats with spontaneous hypertension. 283 46

A nonrecirculatory perfusion system for precision-cut rat liver slices has been developed and utilized for investigating hormone-regulated hepatic glucose metabolism. In this system, slices are cultured in a highly controlled environment and exhibit excellent retention of viability as judged by their maintenance of intracellular potassium and glycogen contents. Using this system, the complex physiological phenomenon of hormone-regulated glycogenolysis was investigated at both extra- and intracellular sites. Specifically, the sensitive responses of intracellular cyclic AMP (cAMP) production, activation of cyclic AMP-dependent protein kinase, and production of glucose upon glucagon stimulation have been measured. The maximal responses observed for these parameters were either equal to or greater than those previously reported for either isolated hepatocytes or perfused livers, demonstrating the sensitivity of this technique. Upon dose-response examination of glucagon challenge, it was observed that high doses of glucagon (greater than 16 nM) stimulate glucose production by activating the cAMP-second messenger cascade. In contrast, low doses (less than 4 nM) stimulate this process without production of intracellular cAMP or activation of cAMP-dependent protein kinase, suggesting the operation of cAMP-independent messenger. Since this system permits measurements of parameters common to many cellular processes, this methodology is suitable for addressing both pharmacological and toxicological questions.
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PMID:Perifused precision-cut liver slice system for the study of hormone-regulated hepatic glucose metabolism. 284 May 33

The role of the plasma membrane in the regulation of lens fiber cell cytosolic Ca2+ concentration has been examined using a vesicular preparation derived from calf lenses. Calcium accumulation by these vesicles was ATP dependent, and was releasable by the ionophore A23187, indicating that calcium was transported into a vesicular space. Calcium accumulation was stimulated by Ca2+ (K1/2 = 0.08 microM Ca2+) potassium (maximally at 50 mM K+), and cAMP-dependent protein kinase; it was inhibited by both vanadate (IC50 = 5 microM) and the calmodulin inhibitor R24571 (IC50 = 5 microM), indicating that this pump was plasma-membrane derived and likely calmodulin dependent. Valinomycin, in the presence of K+, stimulated calcium uptake, suggesting that the calcium pump either countertransports K+, or is regulated in an electrogenic fashion. Inhibition of calcium uptake by selenite and p-chloromercuribenzoate demonstrates the presence of an essential -SH group(s) in this enzyme. Calcium release from calcium-filled lens vesicles was enhanced by Na+, demonstrating that these vesicles also contain a Na:Ca exchange carrier. p-Chloromercuribenzoate and p-chloromercuribenzoate sulfonic acid also promoted calcium release from calcium-filled vesicles, suggesting that this release, like calcium uptake, is in part mediated by a cysteine-containing protein. We conclude that lens fiber cell cytosolic Ca2+ concentration could be regulated by a number of plasma membrane processes. The sensitivity of both calcium uptake and release to -SH reagents has implications in lens cataract formation, where oxidation of lens proteins has been proposed to account for the elevated cytosolic Ca2+ in this condition.
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PMID:Calcium regulation by lens plasma membrane vesicles. 284 Aug 57

The enzymes adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (protein kinase A) and protein kinase C regulate the activity of a diverse group of cellular proteins including membrane ion channel proteins. When protein kinase A was stimulated in cardiac ventricular myocytes with the membrane-soluble cAMP analog 8-chlorphenylthio cAMP (8-CPT cAMP), the amplitude of the delayed-rectifier potassium current (IK) doubled when recorded at 32 degrees C but was not affected at 22 degrees C. In contrast, modulation of the calcium current (ICa) by 8-CPT cAMP was independent of temperature with similar increases in ICa occurring at both temperatures. Stimulation of protein kinase C by phorbol 12,13-dibutyrate also enhanced IK in a temperature-dependent manner but failed to increase ICa at either temperature. Thus, cardiac delayed-rectifier potassium but not calcium channels are regulated by two distinct protein kinases in a similar temperature-dependent fashion.
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PMID:Regulation of a heart potassium channel by protein kinase A and C. 284 75


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