Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vasculature of rat isolated mesentery and small intestine was perfused with a gelatin-containing physiological salt solution (GPSS). When 5-hydroxytryptamine (5HT, 1 x 10(-4) M), or the calcium ionophore A23187 (1 x 10(-4) M), or 12-deoxyphorbol 13-phenylacetate (DOPPA, 1 x 10(-6) M), or 12-deoxyphorbol 13-phenylacetate 20-acetate (DOPPAA, 1 x 10(-6) M) or thymeleatoxin (TMX, 1 x 10(-6) M) was added to the GPSS for 5 min there was a gradual rise in perfusion pressure, whereas resiniferatoxin (RFX, 1 x 10(-6) M) was without effect. Pre-treatment of the tissue with the protein kinase C (PKC) inhibitor Ro 31-8220 (1 x 10(-6) M) significantly reduced the rise in perfusion pressure in response to 5HT, DOPPA, DOPPAA and TMX, but not that to A23187. Platelet-activating factor (PAF, 5 x 10(-6) M) caused an almost immediate but transient rise in perfusion pressure, followed by a more gradual rise, neither response being blocked by Ro 31-8220. When blood vessels of the mesentery alone were perfused with gelatin-free PSS, PAF caused a transient rise in perfusion pressure, but with no subsequent gradual rise over 5 min. After Ca(2+)-depletion this transient response was also absent. In contrast, when blood vessels were perfused with gelatin-free PSS, DOPPA and TMX still caused gradual rises in perfusion pressure, which were totally abolished by Ro 31-8220. TMX had no effect at all when the tissue was depleted of Ca2+, whereas the response to DOPPA was only partially reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Vasoconstriction in rat isolated mesentery and small intestine in response to various activators of protein kinase C. 774 Oct 37

Protein phosphatases PPZ1 and PPZ2 represent a novel form of Ser/Thr phosphatases structurally related to type 1 phosphatases and characterized by an unusual amino-terminal region. We have found that the deletion of PPZ1 gene results in increased tolerance to Na+ and Li+ cations. Simultaneous deletion of PPZ2 gene results in an additional increase in salt tolerance. After exposure to high concentration of Li+, the intracellular content of the cation was markedly decreased in ppz1 delta ppz2 delta mutants when compared to wild type cells. No significant differences were observed between both strains when the Li+ influx was measured, but ppz1 delta ppz2 delta mutants eliminated Li+ more efficiently than wild type cells. This can be explained by the fact that expression of the ENA1 gene, which encodes the major component of the efflux system for these cations, is strongly increased in ppz1 delta ppz2 delta cells. As expected, the disruption of the PPZ genes did not complement the characteristic hypersensitivity for Na+ and Li+ of a ena1 delta strain. The lack of protein phosphatase 2B (calcineurin) has been found to decrease salt resistance by reducing the expression of the ENA1 gene. We have observed that the disruption of the PPZ genes substantially enhances the resistance of the hypersensitive calcineurin-deficient mutants. Since PPZ phosphatases have been found to be functionally related to the protein kinase C/mitogen-activated kinase pathway, we have tested bck1 or mpk1/slt2 deletion mutants and found that they do not display altered salt sensitivity. However, disruption of PPZ1 fails to increase salt resistance in a mpk1/slt2 background. In conclusion, we postulate the existence in yeast of a novel PPZ-mediated pathway involved in salt homeostasis that is opposite to and independent of the recently described calcineurin-mediated pathway.
 ...
PMID:The PPZ protein phosphatases are important determinants of salt tolerance in yeast cells. 776 97

Hormonal activation of protein kinase C (PKC) is a major signaling mechanism regulating salt and water transport in the distal nephron. We used antisense DNA to down-regulate a PKC isoform in the rabbit cortical collecting duct (CCD) and examined its role in mediating arginine vasopressin's (AVP) effect on salt transport in the CCD. Immunoblots demonstrate that PKC-epsilon (diacylglycerol sensitive) and PKC-zeta (diacylglycerol insensitive) are the major PKC isoforms in both freshly isolated and primary cultures of rabbit CCDs. Rabbit CCDs grown on semi-permeable supports, displayed a positive baseline short circuit current (Isc), which was abolished by amiloride, demonstrating active Na+ absorption. Both AVP and 8-chloro-phenylthio-cAMP (8CPTcAMP) transiently increased Isc, however, within 40 min Isc fell below baseline. Down-regulation of PKC-epsilon, as confirmed by immunoblot, was achieved either by treatment with a PKC-epsilon-specific antisense oligonucleotide or 48 h of 1 microM PMA. In PKC-epsilon down-regulated cells, 8CPTcAMP produced a sustained, rather than transient, increase in Isc. We suggest cAMP stimulates Na+ transport, but secondary activation of PKC-epsilon results in the sustained inhibition of Na+ transport seen in response to vasopressin in the CCD.
 ...
PMID:Anti sense DNA down-regulates proteins kinase C-epsilon and enhances vasopressin-stimulated Na+ absorption in rabbit cortical collecting duct. 776 15

The vasculature of the isolated mesentery and small intestine was perfused with a gelatin-containing physiological salt solution in vitro. Various phorbol-related compounds that are known to have different affinities for the protein kinase C (PKC) isoenzymes, and bradykinin (BK), were tested for their ability to cause the microvascular endothelium to become permeable to injected colloidal carbon (CC). Phorbol 12,13-dibutyrate (PDB), 12-deoxyphorbol 13-phenylacetate (DOPPA), thymeleatoxin (TMX), and resiniferatoxin (RFX), each at a concentration of 1 microM, were found to increase permeability. Pretreatment with the PKC inhibitor Ro 31-8220 (1 microM) significantly reduced the response to all of these compounds. Indomethacin (1 microM), on the other hand, reduced only the effect of RFX. 12-Deoxyphorbol 13-phenylacetate 20-acetate (DOPPAA) (1 microM) and BK (10 microM) did not increase CC leakage. These results suggest that the Ca(2+)-dependent PKC alpha-isoenzyme was involved in the increase in endothelial permeability. BK does not appear to stimulate PKC activity in this experimental situation.
 ...
PMID:Stimulation of protein kinase C activity may increase microvascular permeability to colloidal carbon via alpha-isoenzyme. 784 93

The bile salt-stimulated cholesterol esterase is a digestive enzyme synthesized by the acinar cells of the pancreas. Previous results have shown that cholesterol esterase biosynthesis and secretion in the AR42J pancreatoma cells could be increased 3-5-fold by intestinal hormones such as cholecystokinin (CCK). The purpose of the current study is to explore the signalling mechanism by which CCK stimulation of AR42J cells results in increased biosynthesis and secretion of the cholesterol esterase. The results showed that the CCK-induced cholesterol esterase secretion could be mimicked by addition of the Ca2+ ionophore A23187 or by transient incubation of AR42J cells with the protein kinase C activator phorbol 12-myristate 13-acetate (PMA). Cholesterol esterase stimulation by CCK, A23187 and PMA could be abolished by the calcium chelator BAPTA or by specific protein kinase C inhibitors such as chelerythrine. Additionally, prolonged incubation of AR42J cells with PMA to reduce the protein kinase C level, also reduced CCK-stimulated cholesterol esterase secretion to a level similar to that observed in control cells. Taken together, these data suggested that CCK activation of cholesterol esterase secretion may be mediated by a Ca(2+)-dependent protein kinase C pathway, requiring increases in calcium mobilization and activation of protein kinase C.
 ...
PMID:Calcium mobilization and protein kinase C activation are required for cholecystokinin stimulation of pancreatic cholesterol esterase secretion. 788 16

Two neuronal protein kinase C substrates, RC3/neurogranin and GAP-43/neuromodulin, preferentially bind to calmodulin (CaM) when Ca2+ is absent. We examine RC3.CaM and GAP-43.CaM interactions by circular dichroism spectroscopy using purified, recombinant RC3 and GAP-43, sequence variants of RC3 displaying qualitative and quantitative differences in CaM binding affinities, and overlapping peptides that cumulatively span the entire amino acid sequence of RC3. We conclude that CaM stabilizes a basic, amphiphilic alpha-helix within RC3 and GAP-43 under physiological salt concentrations only when Ca2+ is absent. This provides structural confirmation for two binding modes and suggests that CaM regulates the biological activities of RC3 and GAP-43 through an allosteric, Ca(2+)-sensitive mechanism that can be uncoupled by protein kinase C-mediated phosphorylation. More generally, our observations imply an alternative allosteric regulatory role for the Ca(2+)-free form of CaM.
 ...
PMID:Calmodulin stabilizes an amphiphilic alpha-helix within RC3/neurogranin and GAP-43/neuromodulin only when Ca2+ is absent. 789 19

The Na-K-Cl cotransporter of avian salt gland is a membrane-bound 170-kDa protein that is phosphorylated in response to cAMP- and Ca(2+)-dependent secretogogues and is homologous to the Na-K-Cl cotransporter in another Cl-secreting epithelia; the shark rectal gland (Torchia, J., Lytle, C., Pon, D. J., Forbush, B., and Sen, A. K. (1992) J. Biol. Chem. 267, 25444-25450). In the present study we assess the role of Ca2+ and protein kinase C (PKC) activation on the phosphorylation of the Na-K-Cl cotransporter. Although the addition of ionomycin alone did not significantly stimulate cotransporter phosphorylation, concurrent addition of ionomycin plus the tumor promoter phorbol 12-myristate 13-acetate (PMA) resulted in a concentration-dependent increase in phosphorylation. Immunoprecipitation experiments, using a monoclonal antibody which specifically recognizes the cotransporter, suggested that the response to CCh or ionomycin plus PMA was quantitatively similar (5-fold) and was localized exclusively on serine residues. In contrast, when 4 alpha-phorbol was added in the presence of ionomycin, no stimulation was observed. To further assess the involvement of PKC on cotransporter phosphorylation the effects of protein kinase inhibitors were tested. Both staurosporine and calphostin C inhibited phosphorylation of the cotransporter at concentrations known to inhibit PKC, whereas the calmodulin antagonist W-7 had no significant effect. The requirement for Ca2+ was tested further by removing Ca2+ from the incubation medium and stimulating with CCh. Under these conditions, the CCh-stimulated phosphorylation was transient and, furthermore, could be completely inhibited by preloading the cells with the Ca2+ chelator BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid) prior to stimulation. The involvement of protein phosphatases on the phosphorylation of the Na-K-Cl cotransporter was also tested. The addition of okadaic acid stimulated phosphorylation by approximately 3-fold. Taken together these results suggest that the phosphorylation state of the cotransporter involves a dynamic interplay between changes in intracellular Ca2+, PKC, and protein phosphatase activities.
 ...
PMID:Carbachol-stimulated phosphorylation of the Na-K-Cl cotransporter of avian salt gland. Requirement for Ca2+ and PKC Activation. 796 70

A cDNA clone pCZ1, with a 1.1 kb insert, was isolated from a NaCl-adapted tobacco cell cDNA library that encodes an apparently full-length 29 kDa protein (251 amino acids) with a calculated pI of 5.7. The encoded peptide had a high amino acid sequence identity with bovine 14-3-3 protein which was originally found as an abundant protein in the animal central nervous system. Recently, proteins with sequence identity to 14-3-3 protein have also been found in plants, insects and yeast, and appear to have diverse physiological functions. Similar to the bovine brain 14-3-3 protein, the recombinant pCZ1 protein stimulated ADP-ribosylation of protein substrate by ADP-ribosyltransferase from the plant and animal pathogenic bacterium Pseudomonas aeruginosa. This recombinant protein also inhibited protein kinase C activity in vitro. Southern blot analyses indicated that most likely five genes encoding 14-3-3-like proteins are present in tobacco. The pCZ1 cDNA insert hybridized to a single mRNA of 1.1 kb from cultured tobacco cells. The level of this mRNA transcript in tobacco cells was downregulated upon adaptation to NaCl but was unaffected by short-term treatment with NaCl, ABA or ethylene. In tobacco plants, expression of transcript that hybridized to pCZ1 was tissue specific, and was most abundant in roots and flower parts. Monoclonal antibody raised against GF14 protein, a maize protein with substantial sequence identity with 14-3-3 protein detected two bands on SDS-PAGE of total proteins from unadapted tobacco cells and only a single band from cells adapted to NaCl. The GF14 antibody was also used to illustrate that the G-box element of a salt-induced gene is associated with a 14-3-3-type protein.
 ...
PMID:A NaCl-regulated plant gene encoding a brain protein homology that activates ADP ribosyltransferase and inhibits protein kinase C. 800 Apr 27

The regulation of transport in the collecting duct is under multi-hormonal control. Vasopressin stimulates water and cation transport, primarily through a V2/Gs-coupled receptor that activates adenylyl cyclase, which raises cAMP. These stimulatory effects are damped by the action of several hormones, including vasopressin itself, which activate inhibitory G proteins, stimulate phospholipid breakdown, increase prostaglandin production, raise intracellular Ca2+, activate protein kinase C, stimulate tyrosine kinases, and raise cGMP. These inhibitory signals interact with the stimulatory, cAMP-coupled signaling pathway at multiple levels. The balance between these pathways controls net salt and water transport in the collecting duct.
 ...
PMID:Hormonal signaling and regulation of salt and water transport in the collecting duct. 801 Jul 58

Bile salt uptake by hepatocytes is modulated in part by changes in intracellular cyclic AMP. We studied the effect of activation of protein kinase C on cyclic AMP-mediated taurocholate uptake in isolated rat hepatocytes. Both dibutyryl cyclic AMP (2 x 10(-6) mol/L) and glucagon (10(-6) mol/L), which increase intracellular cyclic AMP, enhanced the initial uptake rate of taurocholate into hepatocytes, with maximal increases of 45% to 50% over the basal uptake rate. Vasopressin (10(-9) mol/L), a hormone known to activate protein kinase C, and phorbol-12,13-dibutyrate (10(-5) mol/L) significantly inhibited the glucagon-stimulated increase in taurocholate uptake rate (72% +/- 10% and 105% +/- 13% inhibition, respectively). Basal (unstimulated) taurocholate uptake rate was not affected by vasopressin or phorbol-12,13-dibutyrate. Down-regulation of the glucagon-stimulated transport was rapid and persisted during the 20-min experimental period. Angiotensin II had a similar but more transient inhibitory effect. Vasopressin and phorbol-12,13-dibutyrate suppression of glucagon-stimulated taurocholate uptake rate was not accompanied by diminished cyclic AMP levels. Moreover, vasopressin and phorbol-12,13-dibutyrate inhibited dibutyryl cyclic AMP-stimulated taurocholate uptake rate can be dissociated from alterations in the cyclic AMP levels.
 ...
PMID:Vasopressin and phorbol-12,13-dibutyrate inhibit glucagon- or cyclic AMP-stimulated taurocholate uptake in isolated rat hepatocytes. 802 Aug 86


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