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

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Query: EC:2.7.11.13 (protein kinase C)
49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Superoxide (O2) production and intracellular signal transduction of neutrophils were evaluated in five Holstein dairy calves and five lactating cows. Opsonised zymosan (OPZ)-induced O2 production by neutrophils from neonatal calves was significantly higher (P<0.01) than that of neutrophils of cows, whereas heat-aggregated IgG (H-agg.IgG)- and phorbol myristate acetate (PMA)-induced O2 production of neutrophils were significantly lower (P< or =0.01) than those of cows. To clarify the functional differences of intracellular signal transduction in neutrophils between neonatal calves and cows, the activities of protein kinase C (PKC) and tyrosine phosphorylation were evaluated in OPZ-, H-agg.IgG- and PMA-stimulated neutrophils. Membrane-associated PKC activity of OPZ-stimulated neutrophils from neonatal calves was significantly higher (P<0.05) than that of cows, whereas PKC activity in membrane-associated fractions of H-agg.IgG-stimulated neutrophils from neonatal calves was significantly lower (P<0.05) than that of cows. A significant difference was not found in membrane-associated PKC activity of neutrophils stimulated with PMA between neonatal calves and cows. The amount of tyrosine phosphorylated 100 kDa protein in neutrophils from neonatal calves stimulated with OPZ, H-agg.IgG and PMA were 192.6, 67.8 and 97.2 per cent of those of cows, respectively. These results indicate that complement receptor type 3 (CR3)- and Fc receptor (FcR)-mediated O2 producing activities of neutrophils are clearly different between neonatal calves and cows. This phenomenon may be associated with the age-related changes in intracellular signal transduction of neutrophils including PKC activity and tyrosine phosphorylation of cellular protein.
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PMID:Comparison of superoxide production, protein kinase C and tyrosine kinase activities in neutrophils from neonatal calves and cows. 983 92

FcgammaRIIIb (CD16) is a glycosyl phosphatidylinositol (GPI)-anchored low-affinity IgG receptor, exclusively expressed on human neutrophils. FcgammaRIIIb associates with complement receptor 3 (CR3, Mac-1, CD11b/CD18), which may indirectly link FcgammaRIIIb to the actin cytoskeleton. Upon neutrophil activation, apoptosis, or chemotaxis, FcgammaRIIIb is shed from the cell surface. In all of these events, actin rearrangements play an important role. To establish a role for the actin cytoskeleton in the control of FcgammaRIIIb shedding, we treated human neutrophils with jasplakinolide, an actin-polymerizing peptide. We show that enhanced actin polymerization induces time- and dose-dependent shedding of FcgammaRIIIb. This effect was not restricted to FcgammaRIIIb, because the cell surface expression of CD43, CD44, and L-selectin was also downregulated after induction of actin polymerization. This actin-dependent pathway is staurosporine sensitive but does not appear to involve activation of PKC or CR3. These data show that the actin cytoskeleton can regulate protein ectodomain shedding from human neutrophils.
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PMID:Actin polymerization induces shedding of FcgammaRIIIb (CD16) from human neutrophils. 1004 51

We previously found a novel glycosylphosphatidylinositol (GPI)-anchored glycoprotein designated GPI-80 that modulates complement receptor 3 integrin-dependent adhesion and in vitro transendothelial migration of neutrophils. In this study, we show that antibody-mediated cross-linking of GPI-80 led to rapid tyrosine phosphorylation mainly of a 34-kDa protein (pp34). Chemical inhibitors, such as genistein, sodium orthovanadate, wortmannin, cytochalasin B, Ro 31-8220, and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N',-tetraacetic acid inhibited this response, whereas pertussis toxin had no effect. These findings demonstrate that the tyrosine phosphorylation of pp34 by cross-linking GPI-80 in human neutrophils involves tyrosine kinases, tyrosine phosphatases, phosphatidylinositol 3-kinase, cytoskeleton reorganization, protein kinase C, and cytoplasmic calcium, but not heterotrimeric G proteins.
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PMID:Tyrosine phosphorylation of a 34-kDa protein induced by cross-linking a novel glycosylphosphatidylinositol-anchored glycoprotein (GPI-80) on human neutrophils that may regulate their adherence and migration. 1077 40

In the present studies, we initiated experiments to identify the signal transduction factors involved in activating phagocytosis, oxidative burst, and degranulation following the binding of IgG-opsonized SE to Fc receptors on the surface of avian heterophils. Peripheral blood heterophils were isolated and exposed to known inhibitors of signal transduction pathways for either 20min (chelerythine, genistein, or verapamil) or 120min (pertussis toxin) at 39 degrees C. The cells were then stimulated for 30min at 39 degrees C with SE opsonized with IgG purified from SE-immune chickens. Phagocytosis, luminol-dependent chemiluminescence (LDCL), and beta-D-glucuronidase release were then evaluated in vitro. The G-protein inhibitor, pertussis toxin, the protein kinase C inhibitor, chelerythine, and the Ca(++) channel blocker, verapamil, markedly reduced phagocytosis in a dose responsive manner. Genistein, a tyrosine kinase inhibitor, had no effect on the phagocytosis of the opsonized SE. Both pertussis toxin (66-98%) and verapamil (47-76%) had marked inhibitory effect on LDCL. Chelerythine (13-25%) and genistein (5-25%) had far less biologically significant effects on LDCL. Neither chelerythine nor genistein had a significant effect on degranulation. Verapamil (2-28%) and pertussis toxin (25-29%) had a moderate inhibitory effect on degranulation stimulated by IgG-opsonized SE. As was found with complement receptor mediated activation of heterophils, the binding of Fc receptors by the IgG-SE complex activated distinct signaling pathways that regulate the functional activities of avian heterophils. Pertussis toxin-sensitive, Ca(++)-dependent, G-proteins and protein kinase C-dependent protein phosphorylation play a major role in the phagocytosis of IgG-opsonized SE. Pertussis toxin-sensitive, Ca(++)-dependent, G-proteins appear to regulate LDCL following Fc receptor binding. The signal transduction inhibitors used in these studies did not affect Fc receptor mediated degranulation by avian heterophils.
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PMID:Signal transduction pathways activated by engaging immunoglobulin Fc receptors on chicken heterophils. 1147 85

Systemic candidasis is a life-threatening complication of antibiotic and immunosuppressive therapies and can alter host defense mechanisms through pathways that are poorly understood. Promotion of polymorphonuclear leukocyte (PMN) chemotaxis by beta-glucan towards fMLP or IL-8 gradients demonstrates a fundamental effect on host defenses by pathogenic fungi. The aim of the present study was to determine whether recognition of beta-glucan is sufficient to alter PMN motility in the absence of agonists of G-coupled protein chemotactic receptors. Present findings demonstrate a profound increase in PMN motility by beta-glucan supplementation of a fibronectin substratum in an underagarose migration assay. Motility on beta-glucan included a 3-fold increase in distance of migration, as well as a 5-fold increase in the number of PMNs recruited into the motile phase as compared to motility on fibronectin alone. This promotion of motility is determined by the beta2 integrin complement receptor 3 (CR3) (CD11b/CD18) rather than the beta1 integrin very late antigen 3 (VLA-3), which mediates chemotaxis on beta-glucan-supplemented matrix towards fMLP. PMN motility on beta-glucan-supplemented fibronectin was selectively decreased by inhibitors of pp60 src and ras, whereas motility was promoted by inhibition of p38-MAPK. No effect of these inhibitors was seen on PMNs migrating on fibronectin alone. Migration on beta-glucan-supplemented fibronectin, but not on fibronectin alone, was negatively regulated by protein kinase C (PKC) or cAMP activation. These findings indicate that beta-glucan is sufficient to alter the migratory capacity of PMN in the absence of costimulation by fMLP. Enhanced PMN migration on beta-glucan is mediated through specific integrins and second messenger pathways that are distinct from those utilized by PMNs migrating in the absence of beta-glucan.
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PMID:Increased neutrophil motility by beta-glucan in the absence of chemoattractant. 1177 38

Macrophage-stimulating protein (MSP) promotes the phagocytosis of C3bi-coated erythrocytes by resident peritoneal macrophages, although the mechanism by which this occurs is largely unknown. We show that MSP-induced complement-mediated phagocytosis requires the RON receptor tyrosine kinase and the alphaMbeta2 integrin, as evidenced by the inability of RON-/- and alphaM-/- peritoneal macrophages to augment phagocytosis of complement-coated sheep erythrocytes in response to MSP. MSP stimulation of macrophages results in tyrosine phosphorylation and AKT activation, and inhibitor studies demonstrate a phagocytic requirement for tyrosine kinase and phosphatidylinositol 3-kinase (PI-3K) activity as well as activity of the atypical protein kinase C (PKC) isoform zeta, which localizes to MSP-induced phagosomes containing complement-coated beads. Additionally, MSP augments the ability of peritoneal macrophages to bind to intercellular adhesion molecule-1 (ICAM-1) via the alphaMbeta2 integrin. MSP-induced ICAM-1 adhesion is also dependent on tyrosine kinase activity, PI-3K, and PKC zeta, indicating that these signaling requirements are upstream of complement receptor 3 activation.
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PMID:Activation of CR3-mediated phagocytosis by MSP requires the RON receptor, tyrosine kinase activity, phosphatidylinositol 3-kinase, and protein kinase C zeta. 1277 13

This experiment was performed to clarify the role of extracellular signal-regulated kinase, ERK1/2, in NADPH oxidase-dependent O2- production in rat peritoneal neutrophils. When neutrophils were exposed to N-formyl-methionyl-leucyl-phenylalanine (fMLP) to stimulate an N-formyl peptide receptor, not only the production of O2- but also the activation of ERK1/2 was observed. The translocation of an NADPH oxidase component, p47(phox), from cytosol to membrane also occurred in neutrophils stimulated with fMLP. U0126, an ERK1/2 kinase inhibitor, inhibited both the production of O2- and the translocation of p47(phox) elicited by fMLP. On the other hand, when complement receptor 3 of neutrophils was stimulated with opsonized zymosan (OZ), weaker activation of ERK1/2 than that by fMLP was observed. In this case, U0126 showed no inhibition against the production of O2- and slight inhibition against the translocation of p47(phox). Large inhibition against the OZ-induced production of O2- was only observed in neutrophils treated with GF109203X, a PKC inhibitor. The present study indicates that receptor dependence exists in the ERK1/2 signaling pathway leading to the activation of NADPH oxidase.
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PMID:Extracellular signal-regulated kinase 1/2 is involved in the activation of NADPH oxidase induced by FMLP receptor but not by complement receptor 3 in rat neutrophils. 1286 93

The vasoactive amine histamine is found at high concentrations in the immune and inflammatory tissues. Earlier studies have revealed that histamine regulates the nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent formation of oxygen radicals by phagocytic cells. However, the effects of histamine on intracellular signal transduction mechanisms of relevance to oxidase regulation remain controversial. For this study, we investigated the effects of histamine on NADPH oxidase activity in human neutrophil granulocytes triggered by a lipoxin A4 receptor agonist [the hexapeptide Trp-Lys-Tyr-Met-Val-Met (WKYMVM), a formyl peptide receptor (FPR) agonist (the chemotactic tripeptide formylmethionyl-leucyl-phenylalanine (fMLF)) and an activator of protein kinase C (phorbol myristate acetate (PMA)]. We report that histamine, acting via H2-type histamine receptors (H2R), suppresses NADPH oxidase-dependent formation of oxygen radicals induced by WKYMVM and fMLF but not that induced by PMA. Peptide-induced mobilization of granule-localized complement receptor 3 (CR3) was unaffected by histamine suggesting that the inhibition specifically affected NADPH oxidase activation. Our data suggest that histamine downregulates FPRL1- and FPR-induced NADPH oxidase activity upstream of protein kinase C (PKC) and downstream of the separation of the peptide-induced signal into granule secretion and oxidase activation.
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PMID:Histamine inhibits neutrophil NADPH oxidase activity triggered by the lipoxin A4 receptor-specific peptide agonist Trp-Lys-Tyr-Met-Val-Met. 1295 Jun 78

We have shown that human endothelial cells (EC) are protected against complement-mediated injury by the inducible expression of decay-accelerating factor (DAF). To understand further the importance of DAF regulation, we characterized EC DAF expression on murine EC in vitro and in vivo using a model of glomerulonephritis. Flow cytometry using the monoclonal antibody (mAb) Riko-3 [binds transmembrane- and glycosylphosphatidylinositol (GPI)-anchored DAF], mAb Riko-4 (binds GPI-anchored DAF) and reverse transcription-polymerase chain reaction (RT-PCR), demonstrated that murine EC DAF is GPI-anchored. Tumour necrosis factor-alpha (TNF-alpha) increased EC DAF expression, detectable at 6 hr and maximal at 24-48 hr poststimulation. DAF upregulation required increased steady-state DAF mRNA and protein synthesis. In contrast, no increased expression of the murine complement receptor-related protein-Y (Crry) was seen with TNF-alpha. DAF upregulation was mediated via a protein kinase C (PKC)alpha, phosphoinositide-3 kinase (PI-3 kinase), p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB)-dependent pathway. The increased DAF was functionally relevant, resulting in a marked reduction in C3 deposition following complement activation. In a nephrotoxic nephritis model, DAF expression on glomerular capillaries was significantly increased 2 hr after the induction of disease. The demonstration of DAF upregulation above constitutive levels suggests that this may be important in the maintenance of vascular integrity during inflammation, when the risk of complement-mediated injury is increased. The mouse represents a suitable model for the study of novel therapeutic approaches by which vascular endothelium may be conditioned against complement-mediated injury.
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PMID:Decay-accelerating factor induction by tumour necrosis factor-alpha, through a phosphatidylinositol-3 kinase and protein kinase C-dependent pathway, protects murine vascular endothelial cells against complement deposition. 1451 Dec 40

The aim of this study was to investigate the effects of elevated glucose concentrations on complement receptor- and Fcgamma receptor-mediated phagocytosis in normal human neutrophils. D-Glucose at 15 or 25 mM dose-dependently inhibited both complement receptor- and Fcgamma receptor-mediated phagocytosis, as compared to that at a normal physiological glucose concentration. The protein kinase C (PKC) inhibitors GF109203X and Go6976 both dose-dependently and completely reversed the inhibitory effect of 25 mM D-glucose on phagocytosis. Complement receptor-mediated phagocytosis was dose-dependently inhibited by the cell permeable diacylglycerol analogue 1,2-dioctanoyl-sn-glycerol (DAG), an effect that was abolished by PKC inhibitors. Furthermore, suboptimal inhibitory concentrations of DAG and glucose showed an additive inhibitory effect on complement receptor-mediated phagocytosis. The authors conclude that elevated glucose concentrations can inhibit complement receptor and Fcgamma receptor-mediated phagocytosis in normal human neutrophils by activating PKCalpha and/or PKCbeta, an effect possibly mediated by DAG.
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PMID:Hyperglycemia-induced protein kinase C activation inhibits phagocytosis of C3b- and immunoglobulin g-opsonized yeast particles in normal human neutrophils. 1463 May 74


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