Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The correlation between phospholamban and sarcoplasmic reticulum Ca(2+)-transporting ATPase levels and the magnitude of phospholamban-mediated stimulation of sarcoplasmic reticulum Ca2+ transport was examined in microsomes prepared from rabbit and canine cardiac, slow twitch and fast twitch skeletal muscle. Phospholamban was absent from microsomes prepared from fast twitch skeletal muscle but present at comparable levels in microsomes prepared from cardiac and slow twitch skeletal muscle. Levels of Ca(2+)-transporting ATPase were higher in microsomes prepared from slow twitch skeletal muscle than in microsomes prepared from cardiac muscle, however, and ratios of phospholamban to Ca(2+)-transporting ATPase were several fold greater in microsomes prepared from cardiac muscle than in microsomes prepared from slow twitch skeletal muscle. Stimulation of ATP-dependent Ca2+ transport following phosphorylation of phospholamban by cAMP-dependent protein kinase or incubation with anti-phospholamban monoclonal antibody was observed only in cardiac muscle microsomes. These observations indicate that phospholamban, while present in both cardiac and slow twitch skeletal muscle, may be involved in the hormonal regulation of sarcoplasmic reticulum Ca2+ transport only in the former, and that the lack of phospholamban-mediated stimulation of Ca2+ transport in slow twitch skeletal muscle sarcoplasmic reticulum may result from the lower ratio of phospholamban to Ca(2+)-transporting ATPase in this tissue.
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PMID:Phospholamban-modulated Ca2+ transport in cardiac and slow twitch skeletal muscle sarcoplasmic reticulum. 134 40

It is universally believed that the removal of external sodium ions is without effect on calcium current. We now report that in enzymatically isolated guinea pig ventricular cells, the replacement of external sodium ions with certain other cations causes a 3- to 6-fold increase in peak L-type calcium current. The increase in current is reversibly blocked by L-type calcium-channel antagonists, not mediated by changes in internal calcium, and is inhibited by intracellular 5'-adenylyl imidodiphosphate, a nonhydrolyzable ATP analogue. The effects of sodium removal (and isoproterenol) were almost completely blocked by intracellular application of a specific (peptide) inhibitor of cAMP-dependent protein kinase. These experiments demonstrate a previously unknown effect of sodium ions to modulate calcium-channel phosphorylation via cAMP-dependent protein kinase.
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PMID:Modulation of L-type calcium channels by sodium ions. 137 2

A putative protein kinase gene (PfPK2) has been isolated from the human parasite Plasmodium falciparum by using a mixed oligonucleotide pool which corresponds to a highly conserved region of serine/threonine protein kinases. The complete nucleotide sequence of 5 kb suggests the existence of a second transcriptional unit besides that of the PfPK2 gene, separated by a highly (A+T)-rich region and transcribed in a different orientation. No intron sequence exists in PfPK2. The predicted amino acid sequence of PfPK2 contains features characteristic of eukaryotic serine/threonine protein kinases. Within its putative catalytic domain it shares 33%, 30%, and 28% amino acid identities with rat calcium-calmodulin-dependent protein kinase, human protein kinase C, and bovine cAMP-dependent protein kinase, respectively. Outside the catalytic domain, however, PfPK2 has no homology with regulatory domains of other protein kinases, indicating PfPK2 might be modulated by signals different from those of higher eukaryotes or might be associated with other regulatory subunits. Using a specific antiserum raised in rabbits against a recombinant fragment of the protein expressed in Escherichia coli, PfPK2 was found to be expressed in a stage-specific fashion and mainly localized in the parasitic membrane.
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PMID:Molecular cloning, stage-specific expression and cellular distribution of a putative protein kinase from Plasmodium falciparum. 137 3

Phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR) by cAMP-dependent protein kinase leads to chloride flux in epithelial cells. Is CFTR also required for the calcium-dependent activation of chloride channels? We used antisense oligodeoxynucleotides to CFTR to reduce the expression of CFTR in colonic and tracheal epithelial cells. The antisense oligomers were a pair of adjacent 18-mers complementary to nucleotides 1-18 and 19-36 of CFTR mRNA. Sense and misantisense oligomers served as controls. A 48-h antisense treatment reduced the expression of CFTR protein as assayed by immunoprecipitation and autoradiography to 26% of the level in sense-treated T84 cells. Whole-cell patch clamp revealed that a 48-h antisense treatment of T84 and 56FHTE-8o- fetal tracheal epithelial cells reduced the cAMP-activated chloride current to approximately 10% of that in sense-treated cells. The half-life of functional CFTR is less than 24 h in these cells. In contrast, the calcium-activated chloride current was not affected by antisense treatment. Hence, the cAMP and calcium pathways are separate. CFTR is required for the cAMP pathway but not for the calcium pathway.
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PMID:Antisense oligodeoxynucleotides to the cystic fibrosis transmembrane conductance regulator inhibit cAMP-activated but not calcium-activated chloride currents. 137 20

We studied changes in myofibrillar function and protein profiles after complete global ischemia with anoxia in rat hearts. Hearts were exposed to global ischemia and anoxia (CGI) for 30 or 60 minutes at 37 degrees C, and myofibrils were prepared for measurement of Ca(2+)-dependent Mg(2+)-ATPase activity at pH 7.0 and 6.5. Hearts incubated in cold saline (1 +/- 1 degrees C) and nonincubated hearts served as controls. Maximum ATPase activity was unchanged at pH 7.0 and pH 6.5 in myofibrils from hearts treated with 30 or 60 minutes of CGI. At pH 7.0, the Hill coefficient, which is an index of cooperative interactions among thin-filament proteins, was unchanged after 30 minutes of CGI but was significantly increased after 60 minutes of CGI. A similar trend for increased cooperativity was observed when myofibrillar ATPase activity was measured at pH 6.5 in myofibrils from rat hearts made ischemic for 30 or 60 minutes. Both 30 and 60 minutes of CGI resulted in increased pCa50 values (half-maximally activating free [Ca2+]) at pH 7.0 and pH 6.5. Densitometric analysis of myofibrillar proteins separated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that troponin I and troponin T were degraded during 60 minutes of CGI. Two new protein bands appearing in ischemia-treated myofibrils were identified as partially degraded troponin I and troponin T with Western blots. The troponin I fragment could be phosphorylated by cAMP-dependent protein kinase. In addition, we observed phosphorylation of a protein band that corresponded to myosin light chain-2 in myofibrils from CGI-treated hearts. These results suggest that degradation of thin-filament proteins may contribute to the changes in cooperativity of Ca2+ regulation of ATPase activity observed in the myofibrils from rat hearts exposed to CGI.
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PMID:Alterations in myofibrillar function and protein profiles after complete global ischemia in rat hearts. 153 Nov 86

We have previously demonstrated FSH-induced increases in cytosolic free calcium ion concentrations ([Ca2+]i) in single granulosa cells. We report here on the role of cAMP-dependent protein kinase (PKA) in the FSH-induced [Ca2+]i increase using swine granulosa cells. The R-isomer of cAMP (Rp-cAMPS) and a synthetic peptide containing the active core region of the PKA inhibitor were used as specific inhibitors of PKA. The Rp-cAMPS dose used was effective in completely abolishing FSH-stimulated progesterone production by cultured granulosa cells. However, FSH retained its ability to initiate a calcium signal even in the presence of the cAMP antagonist. In addition, both Rp-cAMPS and the PKA inhibitor peptide significantly reduced the percentage of granulosa cells able to generate [Ca2+]i signals in response to 8-bromo-cAMP without affecting the percentage of [Ca2+]i responses to FSH. We conclude from these observations that at least two aspects, percentage of responding cells and kinetics of the response, of FSH-induced [Ca2+]i increases in swine granulosa cells appear to be independent of the action of PKA. Such findings suggest a direct action of cAMP on [Ca2+]i or cAMP-independent action(s) of FSH in granulosa cells.
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PMID:Is the calcium signal induced by follicle-stimulating hormone in swine granulosa cells mediated by adenosine cyclic 3',5'-monophosphate-dependent protein kinase? 154 16

We have compared and contrasted the abilities of TSH and agents capable of discretely activating the cAMP-dependent protein kinase, protein kinase C, or calcium mobilization to influence the secretion of iodinated compounds from cells prelabeled with iodide and blocked from further organification with methimazole. We found that calcium mobilization induced by A23187, protein kinase C activation induced by 12-O-tetradecanoyl phorbol 13-acetate (TPA) and TSH all stimulated the secretion of iodinated compounds. The effects of TSH were mimicked by forskolin and those of TPA by a synthetic diacylglycerol, sn-1,2-dioctanoylglycerol. The effects of TPA were partially inhibited by staurosporine whereas those of TSH were not. Epidermal growth factor and norepinephrine were without effect on thyroid secretion. The effects of A23187 and TPA were synergistic. The effects of TSH and TPA were not and the increased secretion induced by either agent was partially prevented by the combination. Preincubation of cells with TSH desensitized the cells to further stimulation by TSH but the stimulatory effects of TPA were unaffected. Exposure of cells to medium without calcium also induced loss of iodinated compounds which was partially prevented by TSH or forskolin but not TPA. TSH did not stimulate the rapid production of inositol trisphosphate production. We conclude that the mechanisms by which TSH (through stimulation of cAMP) and stimulators of other intracellular pathways exert their effects on secretion of iodocompounds, differ. Activation of protein kinase C and acute production of inositol trisphosphate do not appear to be involved in the mechanism of action of TSH in stimulating thyroid secretion but calcium mobilization is implicated.
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PMID:Control of thyroid secretion: effects of stimulators of protein kinase C, thyrotropin, and calcium mobilization on secretion of iodinated compounds from sheep thyroid cells. 154 39

Multiple endogenous substrates phosphorylated by four distinct protein kinases were identified in particulate and cytosolic fractions from the larval prothoracic gland of the tobacco hornworm, Manduca sexta. Three prominent particulate-associated phosphoprotein substrates (19, 21, and 34 kDa) were of particular interest. The in vitro phosphorylation of the 19 and 21 kDa peptides was markedly enhanced by cAMP, Ca2+/calmodulin, as well as Ca2+/phospholipids, presumably via cAMP-dependent protein kinase (cAMP-PK), Ca2+/calmodulin-dependent protein kinase (Ca2+/CaM-PK), and protein kinase C (PKC), respectively. The polyamine spermine markedly inhibits both PKC- and cAMP-PK-mediated phosphorylation of the 19 and 21 kDa peptides but had no effect on the Ca2+/CaMP-PK-mediated phosphorylation. Spermine also inhibits the phosphorylation of the 34 kDa peptide via cAMP-PK but does not affect PKC-promoted phosphorylation. In contrast to this differential inhibition of phosphorylation by a polyamine, four cytosolic and three particulate-associated peptides from the prothoracic glands undergo enhanced phosphorylation in the presence of spermine, presumably by stimulating casein kinase II activity. Therefore, polyamines appear to have multiple effects on protein phosphorylation pathways in this important endocrine gland, perhaps representing an important new regulatory control mechanism.
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PMID:Polyamines modulate multiple protein phosphorylation pathways in the insect prothoracic gland. 155 68

Secretion of beta-endorphin from mouse pituitary AtT20 cells is stimulated by a variety of compounds that raise intracellular cAMP and Ca2+. To investigate the role of cAMP-dependent protein kinases in secretion, AtT20 cells were transfected with an expression vector coding for a regulatory (R) subunit of cAMP-dependent protein kinase containing mutations in both cAMP-binding sites. Expression of the mutant regulatory subunit in stable transformants (RAB cells) results in a dominant inhibition of cAMP-dependent protein kinase activity. Isoproterenol (1 microM) or analogs of cAMP stimulated beta-endorphin secretion from AtT20 cells, but failed to stimulate secretion in RAB cells expressing the mutant R subunit. Secretion in response to CRF (100 nM) was inhibited by 80% in these mutant clones, whereas the secretory response to vasoactive intestinal peptide (VIP; 100 nM) or phorbol ester (100 nM phorbol myristate acetate) was not inhibited by the R subunit mutation. Intracellular cAMP was elevated in response to CRF (11- to 15-fold), isoproterenol (5- to 10-fold), and VIP (4- to 8-fold) in RAB cells. Similar concentrations of VIP were required to evoke beta-endorphin secretion in either RAB cells or AtT20 cells. As with most secretagogues, VIP-induced secretion was inhibited in the presence of either EGTA or a voltage-sensitive Ca2+ channel antagonist, PN200-110. The secretory response to VIP was unaffected by down-regulation of protein kinase-C. These results suggest that CRF and isoproterenol work via cAMP-dependent protein kinase to activate beta-endorphin secretion, whereas VIP can act by a different mechanism that does not involve cAMP-dependent protein kinase or protein kinase-C.
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PMID:Role of cyclic adenosine 3',5'-monophosphate-dependent protein kinase in hormone-stimulated beta-endorphin secretion in AtT20 cells. 164 51

Calmodulin-dependent phosphodiesterase was purified to apparent homogeneity from the total calmodulin-binding fraction of bovine heart in a single step by immunoaffinity chromatography. The isolated enzyme had significantly higher affinity for calmodulin than the bovine brain 60-kDa phosphodiesterase isozyme. The cAMP-dependent protein kinase was found to catalyze the phosphorylation of the purified cardiac calmodulin-dependent phosphodiesterase with the incorporation of 1 mol of phosphate/mol of subunit. The phosphodiesterase phosphorylation rate was increased severalfold by histidine without affecting phosphate incorporation into the enzyme. Phosphorylation of phosphodiesterase lowered its affinity for calmodulin and Ca2+. At constant saturating concentrations of calmodulin (650 nM), the phosphorylated calmodulin-dependent phosphodiesterase required a higher concentration of Ca2+ (20 microM) than the nonphosphorylated phosphodiesterase (0.8 microM) for 50% activity. Phosphorylation could be reversed by the calmodulin-dependent phosphatase (calcineurin), and dephosphorylation was accompanied by an increase in the affinity of phosphodiesterase for calmodulin.
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PMID:Phosphorylation and characterization of bovine heart calmodulin-dependent phosphodiesterase. 164 4


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