Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.12 (PKG)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Na+, K+-ATPase activity of homogenates prepared from cauda epididymal golden hamster sperm increased after the addition of cGMP (50 microM), monobutyryl cGMP (0.5 microM) or cGMP-dependent protein kinase (0.94 micrograms/ml). Addition of monobutyryl cAMP (0.5 microM) or purified catalytic subunit of cAMP-dependent protein kinase (1.26 micrograms/ml) inhibited the activity of the Na+, K+-ATPase. Preincubation with a partially purified preparation of cAMP-dependent protein kinase inhibitor (75 micrograms/ml) stimulated the activity of the Na+, K+-ATPase, and this stimulation was decreased by the addition of 5 microM monobutyryl cAMP. It is not yet known whether direct and/or indirect mechanisms are involved, but these results are the first to describe such opposing effects by cyclic nucleotide-mediated processes on a Na+, K+-ATPase activity.
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PMID:Initial evidence for the modification of hamster sperm Na+, K+-ATPase activity by cyclic nucleotide-mediated processes. 630 96

The inter- and intracellular regulator nitric oxide (NO) has been suggested to play a role in the modulation of cellular excitability, but the mechanism(s) by which this occurs remain unclear. Using the kidney as a model system, we report here evidence that NO, produced in response to various hormones and cytokines, can effect long-term alterations in the activity of the membrane sodium pump. This regulation of Na, K-ATPase, which occurs in a system of NO-containing renal tubules, involves cGMP and cGMP-dependent protein kinase. Na, K-ATPase can also be regulated by alterations of cGMP initiated through NO-independent factors, such as atriopeptin, and in nonrenal tissues, such as cerebellum. Regulation of the membrane sodium pump by NO and cGMP, therefore, represents a mechanism for hormonal modulation of ion gradients, not only in kidney but also in other organs, including brain, where NO and cGMP play a prominent role in cellular function.
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PMID:Nitric oxide, cGMP, and hormone regulation of active sodium transport. 752 49

Carbon monoxide (CO) induces a long-lasting alteration in cerebellar alpha 3-Na,K-ATPase independent of [Na+] but linked to cGMP synthesis and localized to Purkinje neurons. The action of CO is absent in Purkinje neuron-deficient mice, mimicked by 8-Br-cGMP, and blocked by inhibition of PKG. Glutamate (Glu) and metabotropic agonists mimic the action of CO, an effect that requires PKC and is associated with CO synthesis. These data suggest that CO regulates Na,K-ATPase through cGMP and PKG, and that Glu regulates CO through mGluRs. This system is also modulated by NMDA agonists and nitric oxide, possibly via Glu release, as well as by free radicals. These findings offer a mechanism by which CO, Glu, and free radicals can exert specific effects on synaptic transmission (relevant to long-term changes in cell excitability), as well as more general actions on energy metabolism (relevant to the pathophysiology of excitotoxicity).
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PMID:The cellular Na+ pump as a site of action for carbon monoxide and glutamate: a mechanism for long-term modulation of cellular activity. 771 40

Phospholamban is a negative regulator of the sarcoplasmic reticulum Ca(2+)-pumping ATPase. Phosphorylation of phospholamban activates the ATPase and decreases the level of cytosolic calcium. Phospholamban is phosphorylated in heart by cAMP-dependent protein kinase, cGMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II (CM-kinase-II) and in smooth muscle cells by cGMP-dependent protein kinase. In contrast to heart muscle, phospholamban is poorly phosphorylated by CM-kinase-II in extracts of rat aortic smooth muscle cells. Rat aorta phospholamban amino acid sequence was identical to dog heart. The peptide substrate specificity of CM-kinase-II from rat aorta was the same as that from rat heart. The lack of phosphorylation of rat aorta phospholamban by the CM-kinase-II appears to result from the relatively low abundance of phospholamban in smooth muscle.
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PMID:Phosphorylation of phospholamban in aortic smooth muscle cells and heart by calcium/calmodulin-dependent protein kinase II. 785 66

Prior studies indicate that the natriuretic effects of atrial natriuretic peptide (ANP) are due, in part, to an inhibition of the passive movement of sodium ions from tubular lumen through apical cation channels into renal tubular epithelium. The present work demonstrates that ANP also exerts a potent inhibitory effect on the active pumping of sodium ions by renal tubular sodium and potassium-activated adenosine triphosphatase (Na, K-ATPase). This action of ANP is relatively long lasting, is due to a change in enzyme Vmax and is specific for ouabain-sensitive activity. Enzyme modulation occurs with an EC50 for ANP of 0.1 nM, is independent of intracellular [Na+] and is associated with an increase in tissue cyclic GMP (cGMP), but not cyclic AMP (cAMP). Modulation of Na, K-ATPase by ANP is mimicked by 8-bromo-cGMP and okadaic acid (OA) and is blocked by KT 5823, a selective inhibitor of cGMP-dependent protein kinase (PKG), but not by KT 5720, a selective inhibitor of cyclic AMP-dependent protein kinase (PKA), which suggests that the action of ANP on the sodium pump involves cGMP-mediated changes in protein phosphorylation. Regulation of renal Na, K-ATPase activity also occurs with nitric oxide-generating compounds, such as nitroglycerin and sodium nitroprusside (SNP). However, the ability of ANP to modulate Na, K-ATPase does not appear to involve this latter pathway because the effects of ANP on the sodium pump cannot be blocked by either N omega-nitro-L-arginine, an inhibitor of NO synthase, or hemoglobin, which blocks NO through binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atrial natriuretic peptide modulates sodium and potassium-activated adenosine triphosphatase through a mechanism involving cyclic GMP and cyclic GMP-dependent protein kinase. 789 13

Paramecium dyneins were tested as substrates for phosphorylation by cAMP-dependent protein kinase, cGMP-dependent protein kinase, and two Ca(2+)-dependent protein kinases that were partially purified from Paramecium extracts. Only cAMP-dependent protein kinase caused significant phosphorylation. The major phosphorylated species was a 29 kDa protein that was present in both 22 S and 12 S dyneins; its phosphate-accepting activity peaked with 22 S dynein. In vitro phosphorylation was maximal at five minutes, then decreased. This decrease in phosphorylation was inhibited by the addition of vanadate or NaF. The 29 kDa protein was not phosphorylated by a heterologous cAMP-dependent protein kinase, the bovine catalytic subunit. Phosphorylation of dynein did not change its ATPase activity. In sucrose gradient fractions from the last step of dynein purification, phosphorylation by an endogenous kinase occurred. This phosphorylation could not be attributed to the small amounts of cAMP- and cGMP-dependent protein kinases known to be present, nor was it Ca(2+)-dependent. This previously uncharacterized ciliary protein kinase used casein as an in vitro substrate.
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PMID:In vitro phosphorylation of ciliary dyneins by protein kinases from Paramecium. 812 14

The 240-kDa, cGMP-dependent protein kinase substrate protein obtained from porcine aortic smooth muscle, whose phosphorylation was closely associated with stimulation of plasma membrane Ca(2+)-pump ATPase (Yoshida, Y., Sun, H.-T., Cai, J.-Q., and Imai, S. (1991) J. Biol. Chem. 266, 19819-19825), was purified to near homogeneity by three successive chromatographic runs with calmodulin-, concanavalin A-, and heparin-Sepharose columns from microsomes solubilized with Triton X-100. The purified protein was found to bind inositol 1,4,5-trisphosphate (InsP3) in a specific, heparin-inhibitable manner with a Kd of 2.0 nM and Bmax of 450 pmol/mg protein (the binding of inositol 1,3,4,5-tetrakisphosphate was much weaker). In sedimentation experiments on a linear sucrose density gradient the InsP3 binding activity was always with the 240-kDa protein. Protein kinase G phosphorylated the InsP3 receptor purified from the rat cerebellum as well as the 240-kDa protein. Sialic acid content of the protein measured with Limulus polyphemus agglutinin was not significantly different from that of the cerebellar InsP3 receptor. Thus, 240-kDa protein closely resembles InsP3 receptor and may be a type of InsP3 receptor. The only difference was the behavior on SDS-polyacrylamide gel electrophoresis. The 240-kDa protein presented itself as two polypeptides with similar but slightly differing M(r) values, both of which were phosphorylated by protein kinase G.
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PMID:Purification and characterization of 240-kDa cGMP-dependent protein kinase substrate of vascular smooth muscle. Close resemblance to inositol 1,4,5-trisphosphate receptor. 815 97

Cyclic GMP (cGMP) mediates vascular smooth muscle relaxation in response to nitric oxide and atrial natriuretic peptides. One mechanism by which cGMP decreases vascular tone is by lowering cytosolic Ca2+ levels in smooth muscle cells. Although mechanisms by which cGMP regulates cytosolic Ca2+ are unclear, an important role for the cGMP-dependent dependent protein kinase in regulating Ca2+ has been proposed. Cyclic GMP-dependent protein kinase has been shown to regulate several pathways that control cytosolic Ca2+ levels: inositol 1,4,5-trisphosphate production and action, Ca(2+)-ATPase ATPase activation, and activation of Ca(2+)-activated K+ channels. The pleiotropic action of cGMP-dependent protein kinase is proposed to occur through the phosphorylation of important proteins that control several signaling pathways in smooth muscle cells. One potential target for cGMP-dependent protein kinase is the class of okadaic acid-sensitive protein phosphatases that appears to regulate K+ channels among other potentially important events to reduce cytosolic Ca2+ and tone. In addition, cytoskeletal proteins are targets for cGMP-dependent protein phosphorylation, and it is now appreciated that the cytoskeleton may play a key role in signal transduction.
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PMID:Pleiotropic regulation of vascular smooth muscle tone by cyclic GMP-dependent protein kinase. 820 4

Calcium ions (Ca2+) are involved in the regulation of many cellular activities. The Ca-ATPase(s) of the plasma membrane and of the endoplasmic reticulum play an important role in controlling the intracellular Ca2+ concentration. Therefore, it is not unexpected that these enzymes are modulated by different factors. The activity of the plasma membrane Ca-ATPase is modified by the amount of negatively charged phospholipids surrounding the enzyme. The regulation of the endoplasmic reticulum Ca-ATPase depends on the phosphorylation of phospholamban by cAMP- and cGMP-dependent protein kinase. These two different Ca2+ transport ATPases are present in both visceral and vascular smooth muscle, but tissue- and species-dependent differences in their relative amount have been observed. In this article we will review the characteristics of Ca-ATPases of the smooth muscle.
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PMID:Plasma membrane and sarcoplasmic reticulum Ca-ATPase and smooth muscle. 893 5

While several studies have investigated the regulation of the Na, K-ATPase consisting of the alpha1 and beta1 subunits, there is little evidence that intracellular messengers influence the other Na pump isozymes. We studied the effect of different protein kinases and arachidonic acid on the rat Na,K-ATPase isoforms expressed in Sf-9 insect cells. Our results indicate that PKA, PKC, and PKG are able to differentially modify the function of the Na,K-ATPase isozymes. While PKC activation leads to inhibition of all isozymes, PKA activation stimulates the activity of the Na,K-ATPase alpha3 beta1 and decreases that of the alpha1 beta1 and alpha2 beta1 isozymes. In contrast, activation of PKG diminishes the activity of the alpha1 beta1 and alpha3 beta1 isozymes, without altering that of alpha2 beta1. Treatment of cells with arachidonic acid reduced the activities of all the isozymes. The changes in the catalytic capabilities of the Na pump isozymes elicited by PKA and PKC are reflected by changes in the molecular activity of the Na,K-ATPases. One of the mechanisms by which PKA and PKC affect Na pump isozyme activity is through direct phosphorylation of the alpha subunit. In the insect cells, we found a PKA- and PKC-dependent phosphorylation of the alpha1, alpha2 and alpha3 polypeptides. In conclusion, several intracellular messengers are able to modulate the function of the Na,K-ATPase isozymes and some of them in a specific fashion. Because the Na,K-ATPase isozymes have kinetic properties that are unique, this isozyme-specific regulation may be important in adapting Na pump function to the requirements of each cell.
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PMID:Differential regulation of Na,K-ATPase isozymes by protein kinases and arachidonic acid. 980 55


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