Dive into the research topics of p21(ras) function is important for T cell antigen receptor and protein kinase C regulation of nuclear factor of activated T cells. Together they form a unique fingerprint. ...
K04166 AGTR1; angiotensin II receptor type 1 K04634 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha K04635 GNA11; guanine nucleotide-binding protein subunit alpha-11 K05858 PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11] K05858 PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11] K05858 PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11] K05858 PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11] K04958 ITPR1; inositol 1,4,5-triphosphate receptor type 1 K04959 ITPR2; inositol 1,4,5-triphosphate receptor type 2 K04960 ITPR3; inositol 1,4,5-triphosphate receptor type 3 K02677 PRKCA; classical protein kinase C alpha type [EC:2.7.11.13] K19662 PRKCB; classical protein kinase C beta type [EC:2.7.11.13] K19663 PRKCG; classical protein kinase C gamma type [EC:2.7.11.13] K18050 PRKCE; novel protein kinase C epsilon type [EC:2.7.11.13] K06070 PKD; protein kinase D [EC:2.7.11.13] K06070 PKD; protein kinase D [EC:2.7.11.13] K06070 PKD; protein ...
TY - JOUR. T1 - Selectivity of connexin 43 channels is regulated through protein kinase C-dependent phosphorylation. AU - Ek-Vitorin, Jose F.. AU - King, Timothy J.. AU - Heyman, Nathanael S.. AU - Lampe, Paul D.. AU - Burt, Janis M.. PY - 2006/6. Y1 - 2006/6. N2 - Coordinated contractile activation of the heart and resistance to ischemic injury depend, in part, on the intercellular communication mediated by Cx43-composed gap junctions. The function of these junctions is regulated at multiple levels (assembly to degradation) through phosphorylation at specific sites in the carboxyl terminus (CT) of the Cx43 protein. We show here that the selective permeability of Cx43 junctions is regulated through protein kinase C (PKC)-dependent phosphorylation at serine 368 (S368). Selective permeability was measured in several Cx43-expressing cell lines as the rate constant for intercellular dye diffusion relative to junctional conductance. The selective permeability of Cx43 junctions under control ...
Complement factor C3, recently found to contain covalently bound phosphate, was phosphorylated in vitro by cyclic AMP-dependent protein kinase (protein kinase A) and Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C). Both protein kinases phosphorylated the same serine residue(s) located in the C3a portion of the alpha-chain. In addition, protein kinase C phosphorylated the beta-chain to a lesser extent. Protein kinase A gave a maximal incorporation of 1 mol of phosphate/mol of C3 while that value with protein kinase C was 1.5 mol of phosphate/mol of C3. The velocity in pmol of [32P]phosphate/(min x unit kinase) was 20 times higher for protein kinase C than for protein kinase A although a 10 times lower ratio of protein kinase to C3 was used in the former case. The apparent Kmfor C3 was 2.6 µM when protein kinase C was used. The phosphorylated C3 was found to be more resistant to partial degradation by trypsin than unphosphorylated C3. It was also found that ...
TY - JOUR. T1 - Identification of a nuclear protein binding element within the rat brain protein kinase C γ promoter that is related to the developmental control of this gene. AU - Chen, Kuang Hua. AU - Widen, Steven. AU - Wilson, Samuel H.. AU - Huang, Kuo Ping. PY - 1993/7/5. Y1 - 1993/7/5. N2 - Protein kinase C γ (PKC γ) is a brain-specific isozyme expressed at a high level in the adult but not in the fetal or newborn rat. At least seventeen nuclear protein binding sites within the 5-flanking region extending from -1612 to +243 had been identified by DNase I footprinting analysis and gel mobility shift assays. Among them, one site, GAATTAATAGG, at -669 to -679 is protected from DNase I digestion by nuclear protein from newborn but not from the adult rat brain. The levels of this binding protein, as determined by gel mobility shift assay, were found inversely related to the levels of PKC γ in rat brain at different stages of development. These results suggest that this particular binding ...
TY - JOUR. T1 - A role for protein kinase C-mediated phosphorylation in eliciting glucagon desensitization in rat hepatocytes. AU - Savage, A.. AU - Zeng, L.. AU - Houslay, M. D.. PY - 1995/4/1. Y1 - 1995/4/1. N2 - An immobilized hepatocyte preparation was used to show that both vasopressin and glucagon could desensitize the ability of glucagon to increase intracellular cyclic AMP concentrations. This process was not dependent on any influx of extracellular Ca2+ and was not mediated by any rise in the intracellular level of Ca2+. The protein kinase C-selective inhibitors chelerythrine, staurosporine and calphostin C acted as potent inhibitors of the desensitization process but with various degrees of selectivity regarding their ability to inhibit the desensitizing actions of glucagon and vasopressin. The protein phosphatase inhibitor okadaic acid was just as potent as vasopressin and glucagon in causing desensitization. Treatment of hepatocyte membranes with alkaline phosphatase restored to near ...
We previously established a cell line from a patient with acute myelomonocytic leukemia with eosinophilia (M4E0), ME-1. ME-1 cells are responsive to colony-stimulating factors (CSFs) such as interleukin-3 (IL-3), IL-4, and granulocyte-macrophage CSF (GM-CSF), and exhibit monocyte-macrophage differentiation. We isolated three subclones, ME-F1 from ME-1, and ME-F2 and ME-F3 from two sublines of ME-1. These subclones had different morphologic, cytochemical, phenotypic, and cytogenetic features. They represented different monocytic-lineage differentiation stages and exhibited different responses to IL-3, GM- CSF, and especially IL-4. IL-3, GM-CSF, and IL-4 enhanced proliferation and differentiation to macrophage-like cells in the ME-F1 subclone. However, they enhanced only proliferation of ME-F2 cells and only differentiation to macrophage-like cells in the ME-F3 subclone. To elucidate possible differences in signal transduction mechanisms in ME- F1, ME-F2, and ME-F3 cells following stimulation by ...
|strong|Mouse anti Human protein kinase C zeta antibody|/strong| recognizes the protein kinase C (PKC) zeta type also known as PKC2.|br||br|Protein kinase C zeta is a member of the PKC family of serin…
TY - JOUR. T1 - Modulation of chemosensitivity in human colon carcinoma cells by downregulating Protein Kinase Cα expression. AU - Chakrabarty, Subhas. AU - Huang, Shuang. PY - 1996/7/1. Y1 - 1996/7/1. N2 - Protein kinase C (PKC) is thought to play a role in tumor progression and drug resistance of colon carcinomas. Specifically, the PKCα isoform has been implicated in drug resistance and responsiveness of colon carcinoma cells to growth factors. Therefore, in this study we determined the effect of downregulating PKCα expression by transfecting human colon carcinoma cells with an antisense PKCα expression vector and then determined the sensitivity of these cells to the anticancer drugs mitomycin C (MMC), 5-fluorouracil (5-FU) and vincristine (Vin). Transiently transfecting the human colon carcinoma cell lines Moser, SW480 and HT29 with antisense PKCα expression vector (but not antisense PKCβ expression vector) consistently increased the sensitivity of these cells to MMC, 5-FU and VIN by ...
TY - JOUR. T1 - Differential effects of protein kinase C inhibitors on chemokine production in human synovial fibroblasts. AU - Jordan, Nicola J.. AU - Watson, Malcolm L.. AU - Yoshimura, Teizo. AU - Westwick, John. PY - 1996. Y1 - 1996. N2 - 1. Rheumatoid arthritis is associated with the accumulation and activation of selected populations of inflammatory cells within the arthritic joint. One putative signal for this process is the production, by resident cells, of a group of inflammatory mediators known as the chemokines. 2. The chemokines interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and RANTES (regulated on activation normal T-cell expressed and presumably secreted) are target-cell specific chemoattractants produced by synovial fibroblasts in response to stimulation with interleukin-1α (IL-1α) or tumour necrosis factor α (TNFα). The signalling pathways involved in their production are not well defined. We therefore used four different protein kinase C inhibitors to ...
TY - JOUR. T1 - Protein kinase C regulates the tonic but not the phasic component of contraction in guinea-pig ileum. AU - Sasaguri, T.. AU - Watson, S. P.. PY - 1989/1/1. Y1 - 1989/1/1. N2 - We have investigated the effect of phorbol esters and the down-regulation of protein kinase C on contraction of guinea-pig ileum longitudinal smooth muscle to carbachol and high K+. Phorbol 12,13-dibutyrate (PDBu) enhanced the phasic component and inhibited or enhanced, respectively, the tonic component of contraction to carbachol and high K+. In contrast, 4α-phorbol, which does not activate protein kinase C, had no effect on these responses. Exposure to phorbol 12-myristate 13-acetate (PMA; 1 μM) for up to 8 h induced a time-dependent loss of [3H]-PDBu binding sites, consistent with the down-regulation of protein kinase C by this treatment. The phasic component of contraction to carbachol or high K+ was unaffected following the down-regulation of protein kinase C. The tonic component of contraction to ...
using yeast to study the role of ceramide pathway in the regulation of mammalian protein kinase c isoforms dissertação de mestrado em genetica molecul
Protein kinase C regulates the activity of a diverse group of cellular proteins including membrane ion channel proteins. Although protein kinase C and its substrate protein have been identified in both membrane and cytosolic fractions in the heart, the physiological role of this kinase in the regulation of cardiac function remains unknown. We examined the physiological role of protein kinase C by stimulating its activity with 12-deoxyphorbol 13 isobutyrate 20 acetate (DPBA) in human trabeculae carneae. This resulted in decreased peak isometric twitch force and peak intracellular sarcoplasmic reticulum calcium release as detected with aequorin. Furthermore, in the presence of DPBA, steady-state force-[Ca2+] relations were shifted to higher intracellular calcium concentrations, and the Hill coefficient was reduced, indicating a decrease in responsiveness of the myofilaments to calcium and a change in cooperativity among thin filament proteins, respectively. Thus, DPBA affects not only ...
wp-content/uploads/2018/08/johns_hopkins_medicine_logo-300-x-156-300x156.jpg 0 0 admin /wp-content/uploads/2018/08/johns_hopkins_medicine_logo-300-x-156-300x156.jpg admin2014-08-08 15:04:382018-08-11 11:48:32Phosphorylation of protein kinase C sites Ser42/44 decreases Ca(2+)-sensitivity and blunts enhanced length-dependent activation in response to protein kinase A in human cardiomyocytes ...
Effects of pentoxifylline and protein kinase C inhibitor on phorbol ester-induced intercellular adhesion molecule-1 expression in brain microvascular endothelial cells.
TY - JOUR. T1 - Inhibition of the spontaneous rate of contraction of neonatal cardiac myocytes by protein kinase C isozymes. T2 - A putative role for the ε isozyme. AU - Johnson, John A. AU - Mochly-Rosen, Daria. PY - 1995/1/1. Y1 - 1995/1/1. N2 - Protein kinase C (PKC) enzymes regulate numerous cardiac functions. In the present study, we determined the effects of the PKC-activating drug 4-β phorbol 12-myristate 13-acetate (4-β PMA) on the rate of contraction and correlated these changes with the distribution and levels of α-, β-, δ-, ε-, and ζ-PKC isozymes by using neonatal rat cardiac myocytes in culture. Treatment with 0.3 to 100 nmol/L 4-β PMA caused negative chronotropic effects on contraction. This effect was maximal at a concentration of 3 nmol/L 4-β PMA and correlated with redistribution of the α- and ε-PKC isozymes from the cytosolic to the particulate cell fraction. After a 1-hour treatment with 100 nmol/L PMA, the α- and β-PKC isozymes and an 80-kD ζ- like PKC isozyme ...
TY - JOUR. T1 - Isolation and characterization of two new Drosophila protein kinase C genes, including one specifically expressed in photoreceptor cells. AU - Schaeffer, Eric. AU - Smith, Dean. AU - Mardon, Graeme. AU - Quinn, William. AU - Zuker, Charles. PY - 1989/5/5. Y1 - 1989/5/5. N2 - We have isolated and characterized two new protein kinase C (PKC) genes from D. melanogaster. One, dPKC98F, maps to chromosome region 98F and displays over 60% amino acid sequence identity with members of a recently described PKC-related subfamily in mammals. The other, dPKC53E(ey), maps to region 53E 4-7 on the second chromosome and lies within 50 kb of a PKC gene previously characterized (dPKC). While dPKC98F transcripts are expressed throughout development, expression of the two genes mapping at cytogenetic location 53E is primarily in adults. dPKC98F and the previously reported 53E gene are transcribed predominantly in brain tissue. In contrast, dPKC53E(ey) is transcribed only in photoreceptor cells. We ...
We found that removal of Ca2+ and inhibition of PKC prevented high Pi-induced O2·− production (Figures 3A and 3B), indicating a role for mechanosensitive Ca2+ signaling and PKC-dependent pathways in high Pi-induced upregulation of NAD(P)H oxidase activity. This idea is consistent with the findings that high Pi elicited significantly greater increases in smooth muscle [Ca2+]i than normal levels of Pi (Figure 4). The important role of Ca2+ signaling is also supported by the finding that administration of a Ca2+ ionophore resulted in significantly increased arterial O2·− production (Figure 3C). Further, pharmacological activation of PKC2 elicited substantial increases in arterial NAD(P)H oxidase-derived O2·− generation (Figure 3C). Because removal of Ca2+ during high-pressure treatment prevented endothelial dysfunction (Figure 1) and increases in O2·− production in high Pi-exposed arteries (Figure 3A) and phorbol ester-stimulated O2·− generation in normotensive arteries could also be ...
This investigation deals with the molecular mechanism of anti-human immunodeficiency virus type 1 (HIV-1) action of pentoxifylline (PTX) [1-(5′-oxohexyl)-3,7-dimethylxanthine] a drug widely used for the treatment of conditions involving defective regional microcirculation. The inhibition by PTX of protein kinase C (PKC) or cAMP-dependent protein kinase (PKA)-mediated activation by phorbol ester (PMA) and tumor necrosis factor alpha (TNF-α) of HIV-1-LTR-regulated reporter gene expression was studied in human CD4+ T lymphocytes (Jurkat) and human embryo kidney cells (293-27-2). A protein kinase C is involved in activation of NF-κB in whole cells, identified by using inhibitors specific for PKC- or PKA-catalyzed NF-κB activation in whole cell and cell-free systems. PTX inhibited PKC- or PKA-catalyzed activation of NF-κB in cytoplasmic extracts from unstimulated Jurkat or 293-27-2 cells, but not interaction of preactivated NF-κB with its motifs. Calphostin C, a specific inhibitor of PKC, inhibited NF
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TY - JOUR. T1 - Photoactivated inhibition of superoxide generation and protein kinase C activity in neutrophils by blepharismin, a protozoan photodynamically active pigment. AU - Watanabe, Yoshiya. AU - E-ige, Keisuke. AU - Kobuchi, Hirotsugu. AU - Kato, Yoji. AU - Matsuoka, Tatsuomi. AU - Utsumi, Toshihiko. AU - Yoshioka, Tamotsu. AU - Horton, Alan A.. AU - Utsumi, Kozo. PY - 1995/2/14. Y1 - 1995/2/14. N2 - Blepharismin is an endogenous photosensitizing pigment found in the protozoan Blepharisma. This pigment inhibited the generation of Superoxide anion (O2-) in neutrophils not only via a diacylglycerol-induced protein kinase C (PKC)-dependent reaction but also by an arachidonate-induced PKC-independent reaction. The inhibition was light and concentration dependent for both reactions. Light-activated inhibition was strong at wavelengths between 520 and 570nm but not above 610nm. PKC activity in neutrophils and from rat brain was inhibited by blepharismin in a light- and concentration dependent ...
TY - JOUR. T1 - Differential effects of protein kinase C on the levels of epithelial Na+ channel subunit proteins. AU - Stockand, James D. AU - Hui-Fang, B.. AU - Schenck, J.. AU - Malik, B.. AU - Middleton, P.. AU - Schlanger, L. E.. AU - Eaton, D. C.. PY - 2000/8/18. Y1 - 2000/8/18. N2 - Regulation of epithelial Na+ channel (ENaC) subunit levels by protein kinase C (PKC) was investigated in A6 cells. PKC activation altered ENaC subunit levels, differentially decreasing the levels of both β and γ, but not αENaC. Temporal regulation of β and γENaC by PKC differed; γENaC decreased with a time constant of3.7 ± 1.0 h, whereas βENaC decreased in 13.9 ±3.0h. Activation of PKC also resulted in a decrease in trans-epithelial Na+ reabsorption for up to 48h. PMA activation of PKC resulted in negative feedback inhibition of PKC protein levels beginning within 4h. Both β and γENaC levels, as well as transport tended toward pretreatment values after 48 h of PMA treatment. PKC inhibitors ...
TY - JOUR. T1 - Synthesis and protein kinase C binding activity of benzolactam-V7. AU - Ma, Dawei. AU - Wang, Guoqiang. AU - Wang, Shaomeng. AU - Kozikowski, Alan P.. AU - Lewin, Nancy E.. AU - Blumberg, Peter M.. PY - 1999/5/17. Y1 - 1999/5/17. N2 - Benzolactam-V7 (3a), a simplified analogues of (-)-indolactam-V with twist-form conformation, was synthesized and evaluated as a new protein kinase C modulator. Both 3a and its-7-substituted analogue 3c showed weak binding activity to displace PDBU binding from recombinant PKCα.. AB - Benzolactam-V7 (3a), a simplified analogues of (-)-indolactam-V with twist-form conformation, was synthesized and evaluated as a new protein kinase C modulator. Both 3a and its-7-substituted analogue 3c showed weak binding activity to displace PDBU binding from recombinant PKCα.. UR - http://www.scopus.com/inward/record.url?scp=0033577690&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0033577690&partnerID=8YFLogxK. U2 - ...
TY - JOUR. T1 - Role of Ras in signal transduction from the nerve growth factor receptor. T2 - Relationship to protein kinase C, calcium and cyclic AMP. AU - Szeberenyi, J.. AU - Erhardt, P.. AU - Cai, H.. AU - Cooper, G. M.. PY - 1992/1/1. Y1 - 1992/1/1. N2 - A dominant inhibitory ras mutant (Ha-ras Asn-17) has been used to investigate the role of Ras in nerve growth factor (NGF)-mediated signal transduction in PC12 cells. Expression of Ha-Ras Asn-17 blocks neuronal differentiation of these cells in response to NGF treatment. The Ha-Ras Asn-17 block was bypassed by treatment with NGF plus dibutyryl cAMP or NGF plus the Ca2+ ionophore ionomycin, but not by NGF plus 12-O-tetradecanoyl phorbol acetate (TPA). Direct stimulation of the cAMP or Ca2+ pathways thus appeared to act synergistically with a Ras-independent NGF signaling pathway. This Ras-independent pathway was also distinct from protein kinase C, since its activity was not affected by protein kinase C down-regulation. It thus appears that ...
Protein Kinase C Theta Type (nPKC Theta or PRKCQ or EC 2.7.11.13) - Pipeline Review, H1 2017 Size and Share Published in 2017-05-30 Available for US$ 3500 at Researchmoz.us
Correlation between endogenous membrane PKC activity and proliferation versus differentiation of normal and HPV16 transformed rat myoblast (L 6 cells): Histochem.J.
Catalytic domain of the Protein Serine/Threonine Kinase, Classical Protein Kinase C. Serine/Threonine Kinases (STKs), Classical (or Conventional) Protein Kinase C (cPKC) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC ...
The activity of calcium-, phospholipid-dependent protein kinase (PKc) was measured in (a) total extracts, (b) crude membrane, and (c) cytosolic fractions of chick embryo myogenic cells differentiating in culture. Total PKc activity slowly declines during the course of terminal myogenesis in contrast to the activity of cAMP-dependent protein kinase, which was also measured in the same cells. Myogenic cells at day 1 of culture possess high particulate and low soluble PKc activity. A dramatic decline of particulate PKc activity occurs during myogenic cell differentiation and is accompanied, through day 4, by a striking rise of the soluble activity. The difference in the subcellular distribution of PKc between replicating myoblasts and myotubes is confirmed by phosphorylation studies conducted in intact cells. These studies demonstrate that four polypeptides whose phosphorylation is stimulated by the tumor promoter 12-O-tetradecanoyl phorbol 13-acetate in myotubes, are spontaneously phosphorylated ...
TY - JOUR. T1 - NMDA receptor blockade prevents the increase in protein kinase C substrate (protein F1) phosphorylation produced by long-term potentiation. AU - Linden, David J.. AU - Wong, Ka L.. AU - Sheu, Fwu Shan. AU - Routtenberg, Aryeh. PY - 1988/8/16. Y1 - 1988/8/16. N2 - Recent evidence has implicated activation of the N-methyl-d-aspartate (NMDA) class of glutamate receptor in the initiation of hippocampal long-term potentiation (LTP), an electrophysiological model of information storage in the brain. A separate line of evidence has suggested that activation of protein kinase C (PKC) and the consequent phosphorylation of it substrates is necessary for the maintenance of the LTP response. To determine if PKC activation is a consequence of NMDA receptor activation during LTP, we applied the NMDA receptor antagonist drug, dl-aminophosphonovalerate (APV) both immediately prior to and following high frequency stimulation, resulting in successful and unsuccessful blockade of LTP initiation, ...
Octadecadienoic acids (linoleic acid and linolelaidic acid) and the diacylglycerol, 1-oleoyl-2-acetyl-rac-glycerol (OAG) concentration-dependently induced activation of gel-filtered human platelets, i.e. aggregation and phosphorylation of 20 kDa and 47 kDa peptides. In contrast, octadecenoic acids (oleic and elaidic acid) and octadecanoic (stearic) acid were inactive. Octadecadienoic acid-induced platelet activation was suppressed by the protein kinase C inhibitor, polymyxin B, but not by the cyclooxygenase inhibitor, indomethacin. OAG-induced activation was potentiated by octadecadienoic acids present at non-stimulatory concentrations. Our data suggest that octadecadienoic acids and diacylglycerol synergistically induce platelet activation via protein kinase C. Furthermore, linolelaidic acid may provide a useful experimental tool to study fatty acid regulation of protein kinase C in intact cells. ...
TY - JOUR. T1 - Properties of membrane-inserted Protein Kinase C. AU - Bazzi, Mohammad D.. AU - Nelsestuen, Gary L.. PY - 1988. Y1 - 1988. N2 - Protein kinase C (PKC) interacted with phospholipid vesicles in a calcium-dependent manner and produced two forms of membrane-associated PKC: a reversibly bound form and a membrane-inserted form. The two forms of PKC were isolated and compared with respect to enzyme stability, cofactor requirements, and phorbol ester binding ability. Membrane-inserted PKC was stable for several weeks in the presence of calcium chelators and could be rechromatographed on gel filtration columns in the presence of EGTA without dissociation of the enzyme from the membrane. The activity of membrane-inserted PKC was not significantly influenced by Ca2+, phospholipids, and/or PDBu. Partial dissociation of this PKC from phospholipid was achieved with Triton X-100, followed by dialysis to remove the detergent. The resulting free PKC appeared indistinguishable from original free ...
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TY - JOUR. T1 - Functional mapping of the promoter region of the GNB2L1 human gene coding for RACK1 scaffold protein. AU - Del Vecchio, Igor. AU - Zuccotti, Annalisa. AU - Pisano, Federica. AU - Canneva, Fabio. AU - Lenzken, Silvia C.. AU - Rousset, Francoise. AU - Corsini, Emanuela. AU - Govoni, Stefano. AU - Racchi, Marco. PY - 2009/2/1. Y1 - 2009/2/1. N2 - RACK1 (Receptor for Activated C Kinase 1) is a scaffold protein for different kinases and membrane receptors. Previously, we characterized an age-dependent decline of RACK1 protein expression which could be counteracted with DHEA (dehydroepiandrosterone) [Corsini, E., et al. 2002. In vivo dehydroepiandrosterone restores age-associated defects in the protein kinase C signal transduction pathway and related functional responses. J. Immunol. 168, 1753-1758. and Corsini, E., et al. 2005. Age-related decline in RACK-1 expression in human leukocytes is correlated to plasma levels of dehydroepiandrosterone. J. Leukoc. Biol. 77, 247-256.]. ...
Translocation of PKC isoforms has been implicated in mechanisms involved in heart failure, 22myocardial hypertrophy, 23and preconditioning. PKC isoforms are activated by phosphorylating enzymes such as G proteins and are modified in enzyme activity by phospholipids, diacylglycerol, increased Ca2+, nitric oxide, and superoxide anions. This is followed by translocation in an isoform-specific and cytoskeleton-mediated manner to subcellular targets, which can be directly visualized by immunohistochemical methods. Only 10 min of ischemia 24or brief administrations of pharmacologic agents 11,25may elicit significant PKC translocation. Recent evidence indicates that translocation is dependent on PKC binding to a family of proteins called receptors of activated C kinase. 26These anchoring proteins are highly specific, and each PKC isoenzyme can bind to only one receptor of activated C kinase. Thus, different PKC isoforms may be linked to distinctive aspects of myocardial function, and this functional ...
The N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor, which plays crucial roles in synaptic plasticity and development. We have recently shown that potentiation of NMDA receptor function by protein kinase C (PKC) appears to be mediated via activation of non-receptor tyrosine kinases. The aim of this study was to test whether this effect could be mediated by direct tyrosine phosphorylation of the NR2A or NR2B subunits of the receptor. Following treatment of rat hippocampal CA1 mini-slices with 500 nM phorbol 12-myristate 13-acetate (PMA) for 15 min, samples were homogenized, immunoprecipitated with anti-NR2A or NR2B antibodies and the resulting pellets subjected to Western blotting with antiphosphotyrosine antibody. An increase in tyrosine phosphorylation of both NR2A (76 +/- 11% above control) and NR2B (41 +/- 11%) was observed. This increase was blocked by pretreatment with the selective PKC inhibitor chelerythrine, with the tyrosine kinase inhibitor Lavendustin A or with the
TY - JOUR. T1 - Unique functions for protein kinase D1 and protein kinase D2 in mammalian cells. AU - Matthews, Sharon A.. AU - Navarro, Maria N.. AU - Sinclair, Linda V.. AU - Emslie, Elizabeth. AU - Feijoo-Carnero, Carmen. AU - Cantrell, Doreen A.. PY - 2010/11/15. Y1 - 2010/11/15. N2 - Mammalian PKD (protein kinase D) isoforms have been implicated in the regulation of diverse biological processes in response to diacylglycerol and PKC (protein kinase C) signalling. To compare the functions of PKD1 and PKD2 in vivo, we generated mice deficient in either PKD1 or PKD2 enzymatic activity, via homozygous expression of PKD1(S744A/S7484) or PKD2(S707A/S711A) knockin alleles. We also examined PKD2-deficient mice generated using gene-trap technology. We demonstrate that, unlike PKD I, PKD2 catalytic activity is dispensable for normal embryogenesis. We also show that PKD2 is the major PKD isoform expressed in lymphoid tissues, but that PKD2 catalytic activity is not essential for the development of ...
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TY - JOUR. T1 - Chromatinized Protein Kinase C-theta: Can It Escape the Clutches of NF-kB?. AU - Sutcliffe, Elissa. AU - Li, Jasmine. AU - Zafar, Anjum. AU - Hardy, Kristine. AU - Ghildyal, Reena. AU - Norris, Nicole. AU - Lim, Chloe (Pek Siew). AU - Milburn, Peter. AU - Casarotto, Marco. AU - Denyer, Gareth. AU - Rao, Sudha. PY - 2012. Y1 - 2012. N2 - We recently provided the first description of a nuclear mechanism used by Protein Kinase C-theta (PKC-θ) to mediate T cell gene expression. In this mode, PKC-θ tethers to chromatin to form an active nuclear complex by interacting with proteins including RNA polymerase II, the histone kinase MSK-1, the demethylase LSD1, and the adaptor molecule 14-3-3ζ at regulatory regions of inducible immune response genes. Moreover, our genome-wide analysis identified many novel PKC-θ target genes and microRNAs implicated in T cell development, differentiation, apoptosis, and proliferation. We have expanded our ChIP-on-chip analysis and have now identified a ...
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We have provided clear evidence that insulin activation of all three signaling components, Viz., IRS-1-dependent PI 3-Kinase, atypical protein kinase C (aPKC) and PKB/Akt is defective in diabetic muscle. These defects are best seen when insulin activation is conducted at both half-maximal and maximal stimulation. Moreover, whereas previous studies had shown that treatment with metformin (Met) alone improves aPKC activation, or that treatment with thiazolidinedione (TZD) alone produces increases in activation of IRS-1/PI3K and aPKC when evaluated at maximal insulin stimulation, we have recently found that combined treatment with Met plus TZD for 6 weeks provokes marked increases in insulin effects on all three signaling factors at both half-maximal and maximal insulin stimulation. This work is being prepared for submission for publication.. We have also evaluated the improvement in insulin signaling in diabetic muscle 4 hours after acute endurance (one-legged) exercise and found that the ...
FIG. 3. Expression of PKC-α, -βI, and -βII isoforms in membrane and cytosolic fractions of DRG in experimental animals. Western blot analysis showed a single band of each isoform in all groups (A). Compared with nondiabetic littermate control mice (Lm) and transgenic mice (Tg), densitometric analysis disclosed reduced expression of membrane α isoform in both diabetic littermate mice (LmDM) and diabetic transgenic mice (TgDM), and the change in diabetic transgenic mice was more severe than in diabetic littermate mice (B). By contrast, cytosolic fraction of α isoform was contrariwise increased to a similar extent in both diabetic transgenic mice and diabetic littermate mice. Treatment with an ARI (fidarestat) corrected these changes in both diabetic groups (LmDM+ARI and TgDM+ARI). There was no change in βI expression in either membrane or cytosolic fraction among all groups. On the other hand, membrane βII expression tended to be elevated in diabetic littermate mice, and the increase was ...
We have isolated and characterized two new protein kinase C (PKC) genes from D. melanogaster. One, dPKC98F, maps to chromosome region 98F and displays over 60% amino acid sequence identity with members of a recently described PKC-related subfamily in mammals. The other, dPKC53E(ey), maps to region …
Protein kinase C has been in the spotlight since the discovery two decades ago that it is activated by the lipid second messenger diacylglycerol. Despite protein kinase Cs enduring stage presence, the regulation and specific roles of its isozymes in defined cellular processes are still under intens …
|p|GF 109203X is a potent and selective inhibitor of protein kinase C [1].|/p||p| Protein kinase C (PKC) is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of serine and threon
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The acetylcholine analogue carbachol rapidly activated mitogen-activated protein kinase (MAPK), and caused tyrosine phosphorylation of the adapter protein p52 Shc and the epidermalgrowth factor (EGF) receptor, in human embryonic kidney cells stably expressing m3 muscarinic receptors. The protein kinase C (PKC) inhibitor GF109203X caused a significant partial inhibition of m3 receptor-mediated activation of MAPK. The PKC-independent MAPK activity elicited by carbachol in the presence of GF109203X was reproducibly abolished by AG1478, an inhibitor of EGF-receptor tyrosine kinase activity, and by the Src tyrosine kinase inhibitor PP1. In a subset of these experiments, GF109203X concomitantly increased carbachol-induced tyrosine phosphorylation of p52 Shc and the EGF receptor. In co-stimulation experiments, carbachol and EGF activated MAPK in a non-additive fashion; moreover, EGF-induced association of Shc with the phosphorylated EGF receptor was inhibited by carbachol. This effect of carbachol was ...
Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins, or a member of this family. PKC enzymes in turn are activated by signals such as increases in the concentration of diacylglycerol (DAG) or calcium ions (Ca2+). Hence PKC enzymes play important roles in several signal transduction cascades. The PKC family consists of fifteen isozymes in humans. They are divided into three subfamilies, based on their second messenger requirements: conventional (or classical), novel, and atypical. Conventional (c)PKCs contain the isoforms α, βI, βII, and γ. These require Ca2+, DAG, and a phospholipid such as phosphatidylserine for activation. Novel (n)PKCs include the δ, ε, η, and θ isoforms, and require DAG, but do not require Ca2+ for activation. Thus, conventional and novel PKCs are ...
TY - JOUR. T1 - Decrease in cytosolic calcium/phospholipid-dependent protein kinase activity following phorbol ester treatment of EL4 thymoma cells. AU - Kraft, A. S.. AU - Anderson, W. B.. AU - Cooper, H. L.. AU - Sando, J. J.. N1 - Copyright: Copyright 2004 Elsevier B.V., All rights reserved.. PY - 1982. Y1 - 1982. UR - http://www.scopus.com/inward/record.url?scp=0020356002&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0020356002&partnerID=8YFLogxK. M3 - Article. C2 - 7142138. AN - SCOPUS:0020356002. VL - 257. SP - 13193. EP - 13196. JO - Journal of Biological Chemistry. JF - Journal of Biological Chemistry. SN - 0021-9258. IS - 22. ER - ...
MARCKS (myristoylated alanine-rich protein kinase C substrate), Authors: Atsuhiro Tanabe, Maho Saito. Published in: Atlas Genet Cytogenet Oncol Haematol.
Phorbol ester-sensitive EL4 murine thymoma cells respond to phorbol 12-myristate 13-acetate with activation of ERK mitogen-activated protein kinases, synthesis of interleukin-2, and death, whereas phorbol ester-resistant variants of this cell line do not exhibit these responses. Additional aspects of the resistant phenotype were examined, using a newly-established resistant cell line. Phorbol ester induced morphological changes, ERK activation, calcium-dependent activation of the c-Jun N-terminal kinase (JNK), interleukin-2 synthesis, and growth inhibition in sensitive but not resistant cells. A series of protein kinase C activators caused membrane translocation of protein kinase Cs (PKCs) alpha, eta, and theta in both cell lines. While PKC eta was expressed at higher levels in sensitive than in resistant cells, overexpression of PKC eta did not restore phorbol ester-induced ERK activation to resistant cells. In sensitive cells, PKC activators had similar effects on cell viability and ERK ...
Looking for online definition of Protein-kinase C-related kinase 2 in the Medical Dictionary? Protein-kinase C-related kinase 2 explanation free. What is Protein-kinase C-related kinase 2? Meaning of Protein-kinase C-related kinase 2 medical term. What does Protein-kinase C-related kinase 2 mean?
Ludwig, L.M.; Weihrauch, D.; Kersten, J.R.; Pagel, P.S.; Warltier, D.C., 2004: Protein kinase C translocation and Src protein tyrosine kinase activation mediate isoflurane-induced preconditioning in vivo: potential downstream targets of mitochondrial adenosine triphosphate-sensitive potassium channels and reactive oxygen species
As the colonic epithelium is physiologically exposed to butyrate and to activators of protein kinase C, we examined the effect of the protein kinase C signalling pathway on butyrate-induced expression of markers of differentiation. Activators and inhibitors of protein kinase C were used in combination with butyrate and effects on the expression of markers of differentiation examined in colon cancer cell lines. When the protein kinase C activator phorbol myristate acetate (100 nM) was added for 24 h prior to the addition of 2 mM butyrate, there was a synergistic increase in alkaline phosphatase activity (154 ± 11% above that for butyrate alone, P = 0.003) in a concentration- and time-dependent manner. Butyrate-induced expression of carcinoembryonic antigen and interleukin-8, dome formation and cell turnover were also markedly augmented by pre-treatment with phorbol myristate acetate. A similar effect was observed with propionate or acetate (but not other differentiating agents), when phorbol ...
Protein kinase C is the Ca{dollar}\sp{lcub}2+{rcub}{dollar}/phospholipid-dependent enzyme that serves as the receptor for, and is directly activated by, the tumour-promoting phorbol esters. To examine the involvement of protein kinase C in the regulation of the organization or function of the actin-containing microfilaments, the activity of the enzyme towards two distinct groups of proteins that are thought to be involved in microfilament regulation has been investigated. For these studies, protein kinase C was partially purified from bovine brain or was more extensively purified from rat brain. Two proteins that are localized in certain areas of microfilament-membrane attachment (focal contacts), vinculin and talin, were identified as in vitro substrates for protein kinase C. Purified protein kinase C also phosphorylated chicken gizzard myosin light chain kinase and different forms of caldesmon, proteins that are involved in the regulation of contractile events. Chicken gizzard caldesmon and chicken
Protein kinase C beta II (PKCβII) has been implicated in diabetic nephropathy (DN). Mesangial cell (MC) hypertrophy is a pathologic feature of DN. PKCβII...
TY - JOUR. T1 - Protein kinase C effects on nerve function, perfusion, Na+,K+-ATPase activity and glutathione content in diabetic rats. AU - Cameron, Norman E. AU - Cotter, M A AU - Jack, A M AU - Basso, M D AU - Hohman, T C PY - 1999. Y1 - 1999. N2 - Aims/hypothesis. Increased protein kinase C activity has been linked to diabetic vascular complications in the retina and kidney, which were attenuated by protein kinase C antagonist treatment. Neuropathy has a vascular component, therefore, the aim was to assess whether treatment with WAY151003 or chelerythrine, inhibitors of protein kinase C regulatory and catalytic domains respectively, could correct nerve blood flow, conduction velocity, Na+,K+-ATPase, and glutathione deficits in diabetic rats.Methods. Diabetes was induced by streptozotocin. Sciatic nerve conduction velocity was measured in vivo and sciatic endoneurial perfusion was monitored by microelectrode polarography and hydrogen clearance. Glutathione content and Na+,K+-ATPase activity ...
TY - JOUR. T1 - Enzastaurin (LY317615), a protein kinase Cβ inhibitor, inhibits the AKT pathway and induces apoptosis in multiple myeloma cell lines. AU - Rizvi, Mujahid A.. AU - Ghias, Kulsoom. AU - Davies, Katharine M.. AU - Ma, Chunguang. AU - Weinberg, Frank. AU - Munshi, Hidayatullah G.. AU - Krett, Nancy L.. AU - Rosen, Steven T.. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2006/7. Y1 - 2006/7. N2 - Enzastaurin (LY317615), an acyclic bisindolylmaleimide, is an oral inhibitor of the protein kinase Cβ isozyme. The objective of this study was to assess the efficacy of enzastaurin in inducing apoptosis in multiple myeloma (MM) cell lines and to investigate possible mechanisms of apoptosis. Cell proliferation assays were done on a variety of MM cell lines with unique characteristics (dexamethasone sensitive, dexamethasone resistant, chemotherapy sensitive, and melphalan resistant). The dexamethasone-sensitive MM.1S cell line was used to further assess the effect ...
Atypical protein kinase C (PKC) isoforms play essential roles in lots of neural processes including synaptic plasticity and neurodegenerative diseases. the appearance of atypical PKCs in phrenic electric MRS 2578 motor neurons offers a construction within which to assess their function in respiratory electric motor control including book types of respiratory plasticity recognized to occur in this area. 2000 Provided their function in synaptic plasticity we questioned whether atypical PKCs can be found in the phrenic electric motor nucleus an integral site for respiratory electric motor plasticity (Mitchell proteins expression thats diminished as well as non-existent (e.g. Sanders and Ridyard 2000 Cell lifestyle circumstances change from the surroundings potentially resulting in altered proteins appearance. The strength of labeling within phrenic electric motor neurons described right here shows that atypical PKC isoforms possess the to be engaged in essential neuron-specific functions like the ...
RESULTS: Pterostilbene possessed comparable antioxidant properties as resveratrol in cell free system. Computational methods were used to establish the molecular characteristics of stilbene derivatives. The values of electronic parameters suggest a slight enhancement of electron donor properties of pterostilbene compared to resveratrol. Phosphorylation and thus activation of protein kinase C alpha/beta II in activated neutrophils was not decreased by pterostilbene. Pterostilbene in concentrations of 10-100 μM was found to inhibit the activity of human caspase-3 purified enzyme and did not influence cell viability significantly ...
TY - JOUR. T1 - Expression of amyloid beta peptide in human platelets. T2 - Pivotal role of the phospholipase Cγ2-protein kinase C pathway in platelet activation. AU - Shen, Ming Yi. AU - Hsiao, George. AU - Fong, Tsorng Han. AU - Chou, Duen Suey. AU - Sheu, Joen Rong. PY - 2008/2. Y1 - 2008/2. N2 - The amyloid β peptide (Aβ), a mediator of neuronal and vascular degeneration in the pathogenesis of Alzheimers disease and cerebral amyloid angiopathy may have peripheral actions. Platelets are enriched with Aβ and have been shown to enhance platelet actions. However, the detailed signaling pathways through which Aβ activates platelets have not been previously explored. In this study, we examined the intra-platelet Aβ distribution using a gold labeling technique and noted that Aβ was predominantly localized in the cytoplasm of resting platelets. A marked increase in Aβ-gold labeling in an open canalicular system was observed in collagen-activated platelets. Exogenous Aβ (2-10 μM) ...
BACKGROUND: Titin is a giant protein crucial for the assembly and elasticity of the sarcomere. Recently, titin has been linked to signal transduction through its kinase domain, which has been proposed to sense mechanical load. We developed a knockout in which expression of M-line-deficient titin can be induced in adult mice and investigated the role of the titin kinase region in cardiac function. METHODS AND RESULTS: Isolated heart experiments revealed that in titin M-line-deficient mice, the contractile response to beta-adrenergic agonists and extracellular calcium is reduced. However, the Ca(2+) sensitivity and cooperativity of activation of skinned cardiac muscle were unchanged. In knockout mice, calcium transients showed a reduced rate of calcium uptake, and expression analysis showed reduced levels of calmodulin, phospholamban, and SERCA2. Ultimately, knockout mice developed cardiac hypertrophy and heart failure, which involves protein kinase C signal transduction but not the ...
TY - JOUR. T1 - Amelioration of denervation-induced atrophy by clenbuterol is associated with increased PKC-alpha activity. AU - Sneddon, Alan Arthur. AU - Delday, Margaret Inkster. AU - Maltin, Charlotte. PY - 2000/7. Y1 - 2000/7. N2 - Rat soleus muscle was denervated for 3 or 7 days, and total membrane protein kinase C (PKC) activity and translocation and immunocytochemical localization of PKC isoforms were examined. Dietary administration of clenbuterol concomitant with denervation ameliorated the atrophic response and was associated with increased membrane PKC activity at both 3 (140%) and 7 (190%) days. Of the five PKC isoforms (alpha, epsilon, theta, zeta, and mu) detected in soleus muscle by Western immunoblotting, clenbuterol treatment affected only the PKC-alpha and PKC-theta forms. PKC-alpha was translocated to the membrane fraction upon denervation, and the presence of clenbuterol increased membrane-bound PKC-alpha and active PKC-alpha as assayed by Ser(657) phosphorylation. PKC-theta ...
Sugita M., Kuwata H., Kudo I., Hara S.. Protein kinase C (PKC) is a family of serine/threonine kinases involved in various signal transduction pathways. We investigated the roles of PKC in the regulation of group IIA secreted phospholipase A(2) (sPLA(2)-IIA) expression in cytokine-stimulated rat fibroblastic 3Y1 cells. Here we show that the induction of sPLA(2)-IIA by proinflammatory cytokines was under the control of both classical cPKCalpha and atypical aPKClambda/iota pathways by using PKC inhibitors, a PKC activator, and PKC knockdowns. Treatment of 3Y1 cells with PKC selective inhibitors having broad specificity, such as chelerythrine chloride and GF109203X, blocked IL-1beta/TNFalpha-dependent induction of sPLA(2)-IIA protein in a dose-dependent manner. Treatment with the PKC activator phorbol 12-myristate 13-acetate (PMA), which activates cPKC and novel nPKC isoforms, markedly attenuated the cytokine-dependent induction of sPLA(2)-IIA expression. In comparison, 24-h pretreatment with PMA, ...
1. Huang KP, Huang FL, Jager T, Li J, Reymann KG, Balschun D. Neurogranin/RC3 enhances long-term potentiation and learning by promoting calcium-mediated signaling. J Neurosci. 2004;24:10660-10669 2. Baudier J, Deloulme JC, Van Dorsselaer A, Black D, Matthes HW. Purification and characterization of a brain-specific protein kinase C substrate, neurogranin (p17). Identification of a consensus amino acid sequence between neurogranin and neuromodulin (GAP43) that corresponds to the protein kinase C phosphorylation site and the calmodulin-binding domain. J Biol Chem. 1991;266:229-237 3. Sheu FS, Mahoney CW, Seki K, Huang KP. Nitric oxide modification of rat brain neurogranin affects its phosphorylation by protein kinase C and affinity for calmodulin. J Biol Chem. 1996;271:22407-22413 4. Cohen RW, Margulies JE, Coulter PM 2nd, Watson JB. Functional consequences of expression of the neuron-specific, protein kinase C substrate RC3 (neurogranin) in Xenopus oocytes. Brain Res. 1993;627:147-152 5. Yang HM, ...
Global Markets Directs, Protein Kinase C Epsilon Type (nPKC Epsilon or PRKCE or EC 2.7.11.13) - Pipeline Review, provides in depth analysis on Protein Kinase C Epsilon Type (nPKC Epsilon or PRKCE or EC 2.7.11.13) targeted pipeline therapeutics.
TY - JOUR. T1 - Phase I trial of high-dose tamoxifen in combination with cisplatin in patients with lung cancer and other advanced malignancies. AU - Perez, Edith A.. AU - Gandara, David R.. AU - Edelman, Martin J.. AU - ODonnell, Robert. AU - Lauder, Ignacio J.. AU - DeGregorio, Michael. PY - 2003/3/18. Y1 - 2003/3/18. N2 - Background. Tamoxifen has been reported to enhance the antitumor activity of cisplatin in preclinical models by modulation of protein kinase C signal transduction and apoptosis-related pathways. Methods. We conducted a phase I study of high-dose oral tamoxifen in combination with intravenous cisplatin, with two objectives: 1) to determine tolerability, and 2) to determine the daily tamoxifen dose required to achieve serum levels equivalent to in vitro concentrations reported to enhance cisplatin cytotoxicity in preclinical models. Tamoxifen was administered days one through seven at escalating daily doses of 160mg/m2 (n = 5), 200mg/m2 (n = 6), and 250 mg/m2 (n = 4) by ...
The Ca2+-insensitive protein kinase C (PKC) isoforms ε, η, δ and ζ are possible direct downstream targets of phosphatidylinositol 3-kinase (PI3-K), and might therefore be involved in insulin signalling. Although isoform-specific changes in PKC expression have been reported for skeletal muscle and liver in insulin-resistant states, little is known about these isoforms in adipocytes. Therefore we studied (1) expression and subcellular localization of these isoforms in murine adipocytes, (2) translocation of specific isoforms to membranes in response to treatment with insulin and phorbol 12-myristate 13-acetate (PMA) and (3) regulation of expression in insulin-resistant states. The PKC isoforms ε, η, δ and ζ are expressed in adipocytes. Immunoreactivity for all isoforms is higher in the membranes than in the cytosol, but subcellular fractionation by differential centrifugation shows an isoform-specific distribution within the membrane fractions. PMA treatment of adipocytes induces ...
Previous studies have shown that activators of protein kinase C (C kinase) produce synaptic potentiation in the hippocampus. For example, the C kinase activator phorbol dibutyrate has been shown to increase transmitter release in the hippocampus. In addition, a role for C kinase in long-term potentiation has been proposed. A common assumption in such studies has been that substrates for C kinase were responsible for producing these forms of synaptic potentiation. However, we have recently shown that phorbol dibutyrate increased the phosphorylated of synapsin II (formerly protein III, Browning et al., 1987) in chromaffin cells (Haycock et al., 1988). Synapsin II is a synaptic vesicle-associated phosphoprotein that is a very poor substrate for C kinase but an excellent substrate for cAMP-dependent and Ca2+/calmodulin-dependent protein kinase. We felt, therefore, that activation of C kinase might lead to activation of a kinase cascade. Thus effects of C kinase activation might be produced via the
TY - JOUR. T1 - The min K channel underlies the cardiac potassium current I(Ks) and mediates species-specific responses to protein kinase C. AU - Varnum, M. D.. AU - Busch, A. E.. AU - Bond, C. T.. AU - Maylie, J.. AU - Adelman, J. P.. PY - 1993. Y1 - 1993. N2 - A clone encoding the guinea pig (gp) min K potassium channel was isolated and expressed in Xenopus oocytes. The currents, gpI(sK), exhibit many of the electrophysiological and pharmacological properties characteristic of gpI(Ks), the slow component of the delayed rectifier potassium conductance in guinea pig cardiac myocytes. Depolarizing commands evoke outward potassium currents that activate slowly, with time constants on the order of seconds. The currents are blocked by the class III antiarrhythmic compound clofilium but not by the sotalol derivative E4031 or low concentrations of lanthanum. Like I(Ks) in guinea pig myocytes, gpI(sK) is modulated by stimulation of protein kinase A and protein kinase C (PKC). In contrast to rat and ...
TY - JOUR. T1 - Phosphorylation of MYPT1 by protein kinase C attenuates interaction with PP1 catalytic subunit and the 20 kDa light chain of myosin. AU - Tóth, Attila. AU - Kiss, Enikö. AU - Gergely, P.. AU - Walsh, Michael P.. AU - Hartshorne, David J.. AU - Erdődi, F.. PY - 2000/11/3. Y1 - 2000/11/3. N2 - The effect of phosphorylation in the N-terminal region of myosin phosphatase target subunit 1 (MYPT1) on the interactions with protein phosphatase 1 catalytic subunit (PP1c) and with phosphorylated 20 kDa myosin light chain (P-MLC20) was studied. Protein kinase C (PKC) phosphorylated threonine-34 (1 mol/mol), the residue preceding the consensus PP1c-binding motif (35KVKF38) in MYPT11-38, but this did not affect binding of the peptide to PP1c. PKC incorporated 2 mol P(i) into MYPT11-296 suggesting a second site of phosphorylation within the ankyrin repeats (residues 40-296). This phosphorylation diminished the stimulatory effect of MYPT11-296 on the P-MLC20 phosphatase activity of PP1c. ...
This study demonstrates that different PKC isoforms are differentially expressed in particular cellular components of ovarian follicles of pre-pubertal, pubertal and adult mouse ovaries.. Data obtained from H-Score evaluation of immunohistochemistry findings revealed that PKCα expression was more apparent in oocytes of all follicles in pre-pubertal, pubertal and adult ovaries, though it was also expressed in granulosa cells. Interestingly, in adult and pre-pubertal ovaries, intense immunostaining of PKCα in oocytes was statistically significant in primordial (PND60, PND7 and PND1), primary (PND60, PND7 and PND1) and secondary follicles (PND60 and PND7), whereas in PND21 ovaries only oocytes of primordial follicles had significantly higher immunostaining level of PKCα. These findings support the idea that PKCα expression in oocytes of larger follicles may have low significance due to granulosa-oocyte interactions during initiation of hormone dependent follicular growth [27],[28]. PKCα ...
We isolated a group of genes that are rapidly and transiently induced in 3T3 cells by tetradecanoyl phorbol acetate (TPA). These genes are called TIS genes (for TPA-inducible sequences). Epidermal growth factor (EGF), fibroblast growth factor (FGF), and TPA activated TIS gene expression with similar induction kinetics. TPA pretreatment to deplete protein kinase C activity did not abolish the subsequent induction of TIS gene expression by epidermal growth factor or fibroblast growth factor; both peptide mitogens can activate TIS genes through a protein kinase C-independent pathway(s). We also analyzed TIS gene expression in three TPA-nonproliferative variants (3T3-TNR2, 3T3-TNR9, and A31T6E12A). The results indicate that (i) modulation of a TPA-responsive sodium-potassium-chloride transport system is not necessary for TIS gene induction either by TPA or by other mitogens and (ii) TIS gene induction is not sufficient to guarantee a proliferative response to mitogenic stimulation. ...
TY - JOUR. T1 - Monoclonal antibody analysis of phosphatidylserine and protein kinase C localizations in developing rat cerebellum. AU - Miyazawa, Atsuo. AU - Inoue, Hiroko. AU - Yoshioka, Tohru. AU - Horikoshi, Tetsuro. AU - Yanagisawa, Keiji. AU - Umeda, Masato. AU - Inoue, Keizo. PY - 1992/10. Y1 - 1992/10. N2 - Understanding the topographical relationships between phosphatidylserine (PS) and protein kinase C (PKC) within neurons can provide clues about the mechanism of translocation and activation of PKC. For this purpose we applied monoclonal antibodies (Abs) of PS and PKC to sections of developing rat cerebellum. The anti-PKC Ab immunohistochemical pattern showed homogeneous staining of Purkinje cells over various postnatal ages, whereas the anti-PS Ab staining showed a heterogeneous localization over these ages. Purkinje cells did not stain well between postnatal day 14 (PND 14) and PND 21, suggesting that the PS was lost from the membrane during preparation of the sections during this ...
Human UC11 astrocytoma cells were used to investigate the role of protein kinase C (PKC) and other kinases in neurokinin (NK)1 receptor desensitization. The selective NK1 receptor agonist [Sar9,Met(O2)11]-substance P stimulated a biphasic accumulation of [3H]inositol phosphates ([3H]IPs) in the presence of 10 mM LiCl in cells that had been prelabeled with [3H]inositol. An initial rapid phase of [3H]IP accumulation during the first 1 min was followed by a slower sustained phase for up to 90 min. These results demonstrate that the human NK1 receptor desensitizes rapidly but only partially. The selective PKC inhibitor Ro31-8220 did not prevent rapid NK1 receptor desensitization but after a longer incubation significantly potentiated human NK1 receptor agonist-stimulated accumulation of [3H]IPs. These results suggest that, although PKC does not mediate the process of rapid desensitization, it does have an inhibitory role at later times. This conclusion is supported by studies with staurosporine, ...
Dynamic changes of glycolipid domains within the plasma membranes of cultured rat cerebellar granule cells have been investigated. For this purpose, a pyrene-labelled derivative of G(M1) ganglioside has been incorporated in the cell plasma membrane, and the rate of excimer formation, directly related to the formation of domains, has been studied by a fluorescence imaging technique (excimer-formation imaging). Fluorescence imaging showed that upon addition of 100 μM glutamate, indirectly inducing the activation of protein kinase C (PKC), glycolipid concentration within domains increases in cell bodies. Comparable effects were exerted by the addition of PMA, directly inducing the activation of PKC. On the contrary, the phorbol ester was not effective in the presence of the specific PKC inhibitor, bisindolylmaleimide. These results suggest that glycolipid-enriched domains are dynamic supramolecular structures affected by membrane-associated events, such as PKC activation. Dynamic changes of ...
0033] In embodiments in which it is desirous to inhibit Hh pathway signaling, a cell is contacted with an aPKC iota antagonist. By an aPKC iota antagonist, it is meant an agent that reduces, suppresses or inhibits aPKC iota activity. In other words, an aPKC iota antagonist antagonizes the activating effect of aPKC iota on the Hh signaling pathway. In some embodiments, the aPKC iota antagonist is a polypeptide or peptide. For example, the antagonist may be a peptide that competes with natural substrates for access to the active site of aPKC iota, i.e. a pseudosubstrate inhibitor, or PSI. In some instance, the PSI is a PSI that is specific for atypical PKCs, i.e. it is specific for aPKC iota and aPKC zeta. In some instances, it is specific for aPKC iota. In some instances, the PSI is a peptide that consists or consists essentially of the sequence SIYRRGARRWRKLY (SEQ ID NO:4), for example a SIYRRGARRWRKLY peptide that has been myristoylated (to make it cell permeable). By consisting essentially ...
BioAssay record AID 163866 submitted by ChEMBL: Inhibition of [3H]- PDBu binding to peptide D of mouse skin Protein kinase C eta (inactive).
2 Department of Radiation Oncology, University Hospital Zurich, CH-8091 Zurich, Switzerland [S. R., C. G., S. B., M. P.]; Laboratory for Biochemistry, Federal Institute of Technology, 8091 Zurich, Switzerland [S. R., K. W.]; Novartis Pharma Inc., 4002 Basel, Switzerland [D. F.]; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 [M. S. S., S. W. L.] Abstract. Caspases are a family of cysteine proteases that constitute the apoptotic cell death machinery. We report the importance of the cytochrome c-mediated caspase-9 death pathway for radiosensitization by the protein kinase C (PKC) inhibitors staurosporine (STP) and PKC-412. In our genetically defined tumor cells, treatment with low doses of STP or the conventional PKC-specific inhibitor PKC-412 in combination with irradiation (5 Gy) potently reduced viability, enhanced mitochondrial cytochrome c release into the cytosol, and specifically stimulated the initiator caspase-9. Whereas treatment with each agent alone had a minimal ...
TY - JOUR. T1 - NF-κB/RelA transactivation is required for atypical protein kinase Cl-mediated cell survival. AU - Lu, Ying. AU - Jamieson, Lee. AU - Brasier, Allan R.. AU - Fields, Alan P.. PY - 2001/8/9. Y1 - 2001/8/9. N2 - In chronic myelogenous leukemia (CML), the oncogene bcr-abl encodes a dysregulated tyrosine kinase that inhibits apoptosis. We showed previously that human erythroleukemia K562 cells are resistant to antineoplastic drug (taxol)-induced apoptosis through the atypical protein kinase C iota isozyme (PKCl), a kinase downstream of Bcr-Abl. The mechanism(s) by which PKCl mediates cell survival to taxol is unknown. Here we demonstrate that PKCl requires the transcription factor nuclear factor-κB (NF-κB) to confer cell survival. At apoptosis-inducing concentrations, taxol weakly induces IκBα proteolysis and NF-κB translocation in K562 cells, but potently induces its transcriptional activity. Inhibition of NF-κB activity (by blocking IκBα degradation) significantly ...
c-Abl and Atm have been implicated in cell responses to DNA damage and oxidative stress. However, the molecular mechanisms by which they regulate oxidative stress response remain unclear. In this report, we show that deficiency of c-Abl and deficiency of ATM differentially altered cell responses to oxidative stress by induction of antioxidant protein peroxiredoxin I (Prx I) via Nrf2 and cell death, both of which required protein kinase C (PKC) δ activation and were mediated by reactive oxygen species. c-abl-/- osteoblasts displayed enhanced Prx I induction, elevated Nrf2 levels, and hypersusceptibility to arsenate, which were reinstated by reconstitution of c-Abl; Atm-/- osteoblasts showed the opposite. These phenotypes correlated with increased PKC δ expression in c-abl-/- osteoblasts and decreased PKC δ expression in Atm-/- cells, respectively. The enhanced responses of c-abl-/- osteoblasts could be mimicked by overexpression of PKC δ in normal cells and impeded by inhibition of PKC δ, and
sn-1,2-Didecanoylglycerol, a synthetic lipid second messenger and model diacylglycerol, was evaluated as a complete skin tumor promoter in CD-1 mice. In addition, sn-1,2-dioctanoylglycerol, sn-1,2-didecanoylglycerol, the second stage tumor promoter mezerein, and the complete tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) were examined for their ability to stimulate epidermal protein kinase C activity in vitro. All four compounds stimulated epidermal protein kinase C activity utilizing lysine-rich histone as the phosphate acceptor substrate. sn-1,2-Dioctanoylglycerol and sn-1,2-didecanoylglycerol stimulated epidermal protein kinase C activity to a maximum velocity similar to that obtained when the enzyme was stimulated with TPA; however, about 1000 times greater concentration of the sn-1,2-diacylglycerols was required. sn-1,2-Didecanoylglycerol was evaluated as a complete skin tumor promoter in CD-1 mice utilizing a dosing regimen demonstrated to produce epidermal hyperplasia. Mice ...
Insulin stimulated protein synthesis in L6 myoblasts but did not increase the labelling of DAG or the release of phosphocholine from phosphatidylcholine. The DAG lipase inhibitor, RHC 80267, more than doubled the amount of label appearing in DAG but did not stimulate protein synthesis. Even in the presence of the DAG lipase inhibitor insulin failed to have any effect on DAG labelling, and conversely RHC 80267 did not modify the insulin-induced increase in protein synthesis. These results suggest that endogenous DAG production is not involved in the stimulation of protein synthesis by insulin. However, exogenous diacylglycerols (1-oleoyl-2-acetyl glycerol and 1-stearoyl-2-arachidonoyl glycerol) both stimulated protein synthesis in L6 myoblasts. The efficacy of the former (arachidonatefree) DAG suggested that their action was by activation of protein kinase C rather than by arachidonate release and prostaglandin formation. Ibuprofen, an inhibitor of cyclo-oxygenase failed to block the effects of ...
TY - JOUR. T1 - PDK1 in apical signaling endosomes participates in the rescue of the polarity complex atypical PKC by intermediate filaments in intestinal epithelia. AU - Mashukova, Anastasia. AU - Forteza, Radia. AU - Wald, Flavia A.. AU - Salas, Pedro J. PY - 2012/5/1. Y1 - 2012/5/1. N2 - Phosphorylation of the activation domain of protein kinase C (PKC) isoforms is essential to start a conformational change that results in an active catalytic domain. This activation is necessary not only for newly synthesized molecules, but also for kinase molecules that become dephosphorylated and need to be refolded and rephosphorylated. This rescuemechanism is responsible for the maintenance of the steady-state levels of atypical PKC (aPKC [PKCι/λ and ζ]) and is blocked in inflammation. Although there is consensus that phosphoinositide-dependent protein kinase 1 (PDK1) is the activating kinase for newly synthesized molecules, it is unclear what kinase performs that function during the rescue and where ...
1. The involvement of phospholipase D (PLD) in the 5-hydroxytryptamine 5-HT1B/5-HT1D-signalling pathway was assessed in the rabbit isolated mesenteric artery. 2. RT-PCR analysis of mesenteric smooth muscle cells revealed a strong signal corresponding to mRNA transcript for the 5-HT1B receptor. The PCR fragment corresponded to the known sequence for the 5-HT1B receptor. No signal corresponding to 5-HT1D mRNA was detected. 3. Neither 5-HT (3 microM) nor KCl (45 mM) individually stimulated any significant increase in the smooth muscle concentration of [33P]-PtdBut to reflect PLD activity. However, in the presence of KCl (45 mM), 5-HT evoked a concentration-dependent increase in [33P]-PtdBut, to a maximum of 84% with 5-HT (3 microM). 4. [33P]-PtdBut accumulation evoked by 5-HT in the presence of KCl was abolished in nominally calcium-free Krebs-Henseleit Buffer (KHB) or with the selective protein kinase C inhibitor, Ro-31 8220 (10 microM, 20 min). 5. 5-HT (3 microM) in the presence of KCl (45 mM) failed to
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Objective: An increase in intracellular calcium concentration ([Ca2+]i) leads to augmentation of late sodium current (late INa) by activating Ca2+-calmodulin-dependent protein kinase II (CaMK-II). The objective of this study was to confirm our hypothesis that both CaMK-II and protein kinase C (PKC) are the signaling molecules whose activation result in increased late INa in the presence of an increased [Ca2+]i.. Methods: Whole-cell and open-cell patch clamp techniques were used to record late INa in rabbit ventricular myocytes dialyzed with pipette solutions containing various concentrations (0.1, 0.3 and 0.6 μM) of [Ca2+]i in the absence and presence of CaMK-II (KN-93), PKC (bisindolylmaleimide, Bim) and MAPK (U0126) inhibitors in the bath solution.. Results: Increases in [Ca2+]i from 0.1 to 0.6 μM resulted in an augmentation of late INa from 0.30 ± 0.03 to 0.45 ± 0.03 pA/pF (n=8-10, p,0.01) in a concentration dependent manner, which was associated with an increase in mean Na+ channel open ...
Pro-apoptotic protein kinase C delta is associated with intranuclear inclusions in a transgenic model of Huntingtons disease.: In order to investigate any effe
In this paper, we have shown that specific isoforms of PKC are pivotal intracellular mediators of signals that regulate the production of rod photoreceptors in the postnatal mouse retina. The complete lack of rods detected in the presence of PKC inhibitors suggests that this enzyme may play this key role for the wide variety of other signals that can elicit rod production.. To provide access to factors that might modulate rod photoreceptor formation, we made use of a well-characterized explant culture system that we developed and have used in many studies of retinal development (Sparrow et al., 1990; Zhao et al., 1995; Zhang et al. 2002, 2004, 2005). These cultures maintain excellent cell viability, tissue lamination, and cell differentiation. In a microarray analysis of gene expression in vivo and in explant cultures, we did, however, find that expression of some genes is delayed by 1-2 d (Liu et al., 2008). This is apparent in the low levels of opsin expression in 4 d explant cultures from P1 ...
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine: A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
TY - JOUR. T1 - Rottlerin inhibits tonicity-dependent expression and action of TonEBP in a PKCδ-independent fashion. AU - Zhao, Hongyu. AU - Tian, Wei. AU - Cohen, David M.. PY - 2002. Y1 - 2002. N2 - Novel protein kinase C (PKC) isoforms PKCδ and PKCε have recently been implicated in signaling by hypertonic stress. We investigated the role of the putative PKCδ inhibitor rottlerin on tonicity-dependent gene regulation. In the renal medullary mIMCD3 cell line, rottlerin blocked tonicity-dependent transcription of a tonicity enhancer (TonE)-driven luciferase reporter gene, as well as tonicity-dependent transcription of the physiological tonicity effector gene aldose reductase, but not urea-dependent transcription. Consistent with these data, rottlerin inhibited tonicity-dependent expression of TonE binding protein (TonEBP) at the mRNA and protein levels. Another inhibitor of both novel and conventional PKC isoforms, GF-109203X, suppressed TonEBP-dependent transcription but failed to influence ...
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipid-dependent protein kinase. This kinase is important for T-cell activation. It is required for the activation of the transcription factors NF-kappaB and AP-1, and may link the T cell receptor (TCR) signaling complex to the activation of the transcription factors.[6]. ...
Protein kinase Cepsilon (PKCε) exerts a well-known cardio-protective activity in ischemia-reperfusion injury and plays a pivotal role in stem cell proliferation and differentiation. Although many studies have been performed on physiological and morphological effects of PKCε mis-expression in cardiomyocytes, molecular information on the role of PKCε on early cardiac gene expression are still lacking. We addressed the molecular role of PKCε in cardiac cells using mouse cardiomyocytes and rat bone marrow mesenchymal stem cells. We show that PKCε is modulated in cardiac differentiation producing an opposite regulation of the cardiac genes NK2 transcription factor related, locus 5 (nkx2.5) and GATA binding protein 4 (gata4) both in vivo and in vitro. Phospho-extracellular regulated mitogen-activated protein kinase 1/2 (p-ERK1/2) levels increase in PKCε over-expressing cells, while pkcε siRNAs produce a decrease in p-ERK1/2. Indeed, pharmacological inhibition of ERK1/2 rescues the expression ...