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)

Acinar cells from guinea pig pancreas possess two distinct protein kinase activities. Cyclic GMP-dependent kinase elutes as a single peak on diethylaminoethyl (DEAE)- cellulose chromatography, is not inhibited by protein kinase inhibitor, and has a greater affinity for cyclic GMP (half-maximal activation at 20 nM) than for cyclic AMP (half-maximal activation at 100 nM). Cyclic AMP-dependent kinase elutes as two peaks on DEAE-cellulose chromatography, is inhibited by protein kinase inhibitor, and has a greater affinity for cyclic AMP (half-maximal activation at 20 nM) than for cyclic GMP (half-maximal activation at 7 micrometer). Binding of cyclic 3H-nucleotides to the enzyme preparation was rapid, specific, temperature-dependent, and reversible, and there was a close correlation between the ability of a particular cyclic nucleotide to inhibit binding of cyclic 3H-nucleotide and its ability of a particular cyclic nucleotide to inhibit binding of cyclic H-nucleotide and its ability to activate protein kinase. Binding of cyclic 3H--nucleotide could not be described as a simple bimolecular reaction and native cyclic nucleotides accelerated the dissociation of bound, labeled cyclic nucleotide. Vasoactive intestinal peptide or secretin, each of which increases cellular cyclic AMP, caused endogenous activation of protein kinase and inhibition of cyclic [3H]AMP binding but did not alter bindings of cyclic [3H]GMP or cyclic [3H]AMP.
...
PMID:Cyclic nucleotide-dependent protein kinase activity in acinar cells from guinea pig pancreas. 21 41

1. Agonists known to increase cyclic AMP levels in gastrointestinal smooth muscles were studied in isolated circular muscles of the canine antrum to investigate the mechanisms of the inhibitory effects of these agents. 2. Muscles were electrically active, generating typical slow wave activity. Cytosolic Ca2+ ([Ca2+]cyt; measured by Indo-1 fluorescence) and tension increased in response to slow waves. 3. Stimulation by isoprenaline (via beta 2-receptors) or forskolin, in the presence or absence of acetylcholine, inhibited the plateau phase and reduced phasic [Ca2+]cyt and contractile responses. 4. Vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP), had similar effects to isoprenaline and forskolin. 5. Increases in the plateau phase of slow waves and the associated increases in [Ca2+]cyt and tension caused by direct activation of voltage-dependent Ca2+ channels by Bay K 8644 (0.1 microM) were also reduced by forskolin. 6. Isoprenaline and forskolin induced negative chronotropic effects, but VIP increased frequency. 7. At a given level of [Ca2+]cyt, contractions were greater under control conditions than in the presence of isoprenaline, VIP and CGRP, suggesting that part of the inhibition produced by these agents may be due to decreased Ca2+ sensitivity of the contractile apparatus. 8. Experiments performed on alpha-toxin-permeabilized muscles confirmed that cyclic AMP-dependent effects involve reduced Ca2+ sensitivity of the contractile apparatus. Addition of cyclic AMP (3-300 microM) caused a reduction in Ca(2+)-induced contraction at a constant level of Ca2+ (pCa 5.5). 9. These results suggest that increased cyclic AMP and probably subsequent activation of protein kinase A: (i) decrease [Ca2+]cyt and contraction by an inhibition of Ca2+ influx during slow waves, and (ii) decrease the sensitivity of the contractile apparatus to [Ca2+]cyt. The membrane effects might occur directly by inhibition of Ca2+ channels or indirectly by increasing the open probability of K+ channels which would tend to cause premature repolarization of slow waves.
...
PMID:Cyclic AMP-mediated regulation of excitation-contraction coupling in canine gastric smooth muscle. 131 33

Many studies suggest that smooth muscle relaxation caused by beta-adrenergic agents and various neuropeptides occurs as a result of an increase in cellular adenosine 3',5'-cyclic monophosphate (cAMP). However, the evidence is indirect, and furthermore does not demonstrate that an increase in cAMP is essential for mediating relaxation. To define more clearly the role of cAMP in receptor-mediated smooth muscle relaxation, we used a specific competitive antagonist of the action of cAMP on protein kinase A, (R)-p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS], and its S isomer, (S)-p-cAMPS, which functions as a cAMP agonist. In gastric smooth muscle cells from guinea pig, (S)-p-cAMPS caused a dose-related relaxation [50% inhibitory concentration (IC50) 86 +/- 59 nM]. Vasoactive intestinal peptide (VIP) produced smooth muscle cell relaxation (IC50 2.3 +/- 0.8 nM) through occupation of specific VIP receptors. (R)-p-cAMPS inhibited VIP-induced relaxation, with a rightward shift in the VIP dose-response curve, suggesting competitive antagonism. Furthermore, (R)-p-cAMPS inhibited relaxation induced by other agents that increase cellular cAMP (isoproterenol, calcitonin gene-related peptide, and glucagon) but not that induced by ATP or sodium nitroprusside. (R)-p-cAMPS had no effect on contraction stimulated by carbachol, cholecystokinin, or substance P. These data demonstrate that activation of protein kinase A is primarily responsible for mediating gastrin smooth muscle relaxation produced by adrenergic agents and various neuropeptides.
...
PMID:A primary role for protein kinase A in smooth muscle relaxation induced by adrenergic agonists and neuropeptides. 132 27

The rat pituitary cell line GH3 contains a high molecular weight microtubule-associated protein with properties characteristic of microtubule-associated protein-2 (MAP-2). The 280-kDa protein is selectively immunoprecipitated by antibodies to authentic bovine brain MAP-2 and is phosphorylated at appropriate sites by cAMP-dependent protein kinase (cAMP kinase) and multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase). Although MAP-2 is a minor cellular constituent, it can be immunoprecipitated from [32P]Pi-labeled GH3 cells and shown to contain a high level of basal phosphorylation. Vasoactive intestinal peptide, forskolin, 3-isobutyl-1-methylxanthene, or cholera toxin, treatments which increase cellular cAMP levels, or dibutyryl cAMP stimulate phosphorylation of specific sites on MAP-2 without significantly increasing its high state of basal phosphorylation. Phosphopeptide mapping reveals that the sites phosphorylated by cAMP kinase in vitro are the same sites whose phosphorylation in situ increases following stimulation of GH3 with agents that activate cAMP kinase. Increasing intracellular Ca2+ levels in GH3 cells also stimulates phosphorylation of MAP-2 but at sites distinct from those phosphorylated following treatment with cAMP inducing agonists. Phosphopeptide mapping indicates that the sites phosphorylated by CaM kinase in vitro are the same sites whose phosphorylation in situ increases following Ca2(+)-mediated stimulation. We conclude that activation of cAMP- and Ca2(+)-based signaling pathways leads to phosphorylation of MAP-2 in GH3 cells and that cAMP kinase and CaM kinase mediate phosphorylation by these pathways, respectively.
...
PMID:Phosphorylation of microtubule-associated protein-2 in GH3 cells. Regulation by cAMP and by calcium. 170 24

Vasoactive intestinal peptide (VIP) induces phosphorylation of a basic 38,000 mol. wt protein in a human lymphoblastic cell line (Molt 4b) and a human colon carcinoma cell line (HT29). In both cell types, VIP interacts with specific high affinity receptors to activate adenylate cyclase and cAMP-dependent protein kinase. The two cell types appear to express homologous receptors with similar affinity and specificity for VIP, but the colonic epithelial cells express a greater number of receptors. HT29 colonic cells also exhibit a greater stimulation of adenylate cyclase and a higher phosphorylation index for the 38,000 mol. wt protein in response to VIP. This 38,000 mol. wt protein, which is phosphorylated in the presence of VIP, appears to be identical in both cell lines; it is phosphorylated in both lymphoblasts and colonic epithelial cells in the presence of forskolin, but not in the presence of phorbol 12-myristate 13-acetate. Phosphorylation of this 38,000 mol. wt protein may be an important step in VIP regulation of water and electrolyte secretion from colonic epithelial cells, and in VIP regulation of immunoglobulin and lymphokine secretion from lymphocytes.
...
PMID:Comparison of vasoactive intestinal peptide-mediated protein phosphorylation in human lymphoblasts and colonic epithelial cells. 277 Jul 50

Vasoactive intestinal peptide stimulated cyclic AMP-dependent protein kinase activity in human blood mononuclear cells. The simultaneous presence of a phosphodiesterase inhibitor was required to elicit maximal activation. The apparent Ka value of half the maximal stimulation was about 60 pmol. Secretin exhibited a 170-times lower potency. Other peptides such as glucagon or insulin had no effect even at 1 microM.
...
PMID:Activation of cyclic AMP-dependent protein kinase by VIP in blood mononuclear cells. 620 83

Vasoactive intestinal peptide (VIP), secretin, catecholamines and prostaglandin E1 (PGE1) in the presence of a cyclic nucleotide phosphodiesterase inhibitor stimulate the accumulation of cyclic AMP in two colorectal carcinoma cell lines (HT 29 and HRT 18) with subsequent activation of the cyclic AMP-dependent protein kinases. In HT 29 cells incubated without phosphodiesterase inhibitor, 10(-9) M VIP promotes a rapid and specific activation of the lower Km cyclic AMP phosphodiesterase (1.7-fold); at 25 degrees C the effect is maintained for more than 15 min, while at 37 degrees C the activity returns to basal value within 15 min. As shown by dose-response studies, VIP is by far the most effective inducer (Ka equals 4 x 10(-10) M) of the cyclic AMP phosphodiesterase activity; partial activation of the enzyme is obtained by 3 x 10(-7) M secretin, 10(-5) M isoproterenol and 10(-5) M PGE1; PGE2 and epinephrine are without effect. In HRT 18 cells VIP is less active (Ka equals 2 x 10(-9) M) whereas 10(-6) M PGE1, 10(-6) M PGE2 and 10(-5) M epinephrine are potent inducers of th phosphodiesterase activity. The positive cell response to dibutyryl-cyclic AMP further indicates that cyclic AMP is a mediator in the phosphodiesterase activation process. The incubation kinetics and dose response effects of the various agonists on the cyclic AMP-dependent protein kinase activity determined for both cell types in the same conditions show a striking similarity to those of phosphodiesterase. Thus coordinate regulation of both enzymes by cyclic AMP was observed in all incubation conditions.
...
PMID:Parallel activation of cyclic AMP phosphodiesterase and cyclic AMP-dependent protein kinase in two human gut adenocarcinoma cells (HT 29 and HRT 18) in culture, by vasoactive intestinal peptide (VIP) and other effectors activating the cyclic AMP system. 626 79

Vasoactive intestinal peptide (VIP) is a neuropeptide that induces neuronal differentiation through a cAMP-dependent mechanism. We have previously shown that VIP induces tyrosine phosphorylation and activation of MAP kinases in PC12h cells [J. Biochem. 115, 304-308 (1994)]. In the present study, we showed by Western blotting with anti-phosphotyrosine antibodies that in PC12h cells VIP induced tyrosine phosphorylation of proteins of 140, 120, 110, and 70 kDa in addition to MAP kinases. The immunoprecipitates with anti-phosphotyrosine antibody from VIP-treated cells contained high activity of protein kinase phosphorylating poly(glu-tyr) and enolase; the activity from VIP-stimulated cells was 1.5-2 times higher than that from unstimulated cells. In vitro kinase reaction without extrinsic substrates resulted in tyrosine phosphorylation of doublet proteins which migrated slower than pp125FAK on SDS-PAGE. An increase in kinase activity of the immunecomplex was detected when the cells were stimulated with forskolin. These results suggest that protein tyrosine phosphorylation is involved in differentiation of neuronal cells stimulated by VIP and that it is regulated by a cAMP-dependent mechanism.
...
PMID:Vasoactive intestinal peptide induces tyrosine phosphorylation in PC12h cells. 782 52

In this study we analysed the involvement of the cAMP-protein kinase-A system in the regulation of interleukin 6 production by cultured cortical astrocytes. Vasoactive intestinal peptide strongly increased, in a dose-dependent manner, interleukin 6 production. This effect was reduced when protein kinase A was blocked by KT-5720; it was not affected by calphostin C, a protein kinase C inhibitor. Forskolin caused a concentration-dependent increase in interleukin 6 release, that was also inhibited by KT-5720. Since prostaglandins are believed to play a role in interleukin 6 production, we tried to determine whether the stimulatory effects of vasoactive intestinal peptide and forskolin on cytokine release might be mediated by stimulation of prostaglandin production in cortical astrocytes. Vasoactive intestinal peptide did not increase the production of either prostaglandin E2 or F2 alpha. Conversely, forskolin concentration-dependently stimulated the production of both prostaglandins, an effect that was blocked by indomethacin. Indomethacin did not affect either vasoactive intestinal peptide- or forskolin-stimulated interleukin 6 production. To exclude the possibility that prostaglandins participate in interleukin 6 production induced by forskolin, we tested the effect of prostaglandins E2 and F2 alpha on the cytokine production. The former was completely ineffective in eliciting the cytokine production, while prostaglandin F2 alpha slightly increase interleukin 6 only at the highest concentration. 8-Br-cAMP and (BU)2- cAMP stimulated interleukin 6 production to a lesser extent than vasoactive intestinal peptide and forskolin. In conclusion, we provide evidence that vasoactive intestinal peptide increases interleukin 6 production by astrocytes through the stimulation of the cAMP-protein kinase-A pathway, an effect that is reproduced by cAMP analogues. In addition, we point out that prostaglandins are not involved in vasoactive intestinal peptide- and forskolin-mediated induction of interleukin 6 production in cultured astrocytes.
...
PMID:Regulation of interleukin 6 production by cAMP-protein kinase-A pathway in rat cortical astrocytes. 783 Nov 91

Vasoactive intestinal peptide (VIP) is widely recognized as a regulator of tyrosine hydroxylase via a mechanism of trans-synaptic activation. Subsets of adrenal medullary cells and postganglionic sympathetic nerves coexpress the peptide neurotransmitter neuropeptide Y (NPY) with catecholamines. Using PC12 cells transiently expressing a fusion gene in which the bacterial enzyme chloramphenicol acetyltransferase (CAT) is under the control of 700 base pairs of the 5' flanking region of the NPY gene, we have studied the role of VIP and the related peptide pituitary adenylate cyclase activating peptide (PACAP) in regulating NPY gene transcription. Both VIP and PACAP stimulated expression of the NPY gene through activation of cAMP-dependent protein kinase. PACAP was 1000-fold more potent in eliciting this response compared to VIP and activity resided in its N-terminal 27 amino acids. Both VIP and PACAP caused a subpopulation (approximately 50%) of PC12 cells to undergo profound morphological changes in that the cells extended long, slender neurites with prominent growth cones. This change in morphology was unaffected by preincubating cells with inhibitors of either cAMP-dependent protein kinase or calcium/phospholipid-dependent protein kinase. A trophic role for either VIP or PACAP in regulating sympathetic nerve function is proposed.
...
PMID:Vasoactive intestinal peptide stimulates neuropeptide Y gene expression and causes neurite extension in PC12 cells through independent mechanisms. 796 4


1 2 3 4 5 Next >>

---