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)

The accumulation of blood monocytes at sites of predilection of the vessel wall is an early cellular event of atherogenesis. Proteins of the vessel wall may facilitate monocyte adhesion and thus promote their recruitment. It has been shown that the relative content of extracellular fibrinogen increases during lesion development, and this study investigated the contribution of immobilized fibrinogen to monocyte adhesion and the underlying mechanism. Freshly isolated human blood monocytes were cultivated in serum-free RPMI 1640 in tissue culture wells precoated with albumin, fibrinogen, or fibrin. After 16 h the plates were washed and adherent cells enumerated. Immobilized fibrinogen enhanced monocyte adhesion more than 1.9-fold compared to immobilized albumin or fibrin (P < 0.05). Concomitant addition of the protein kinase C (PKC) inhibitors staurosporine or H7 suppressed monocyte adherence to immobilized fibrinogen but exerted no significant effect upon adhesion to any other surface tested. Stimulation of monocytes using phorbol myristate acetate resulted in increased binding of monocytes on fibrinogen but not on bovine serum albumin. When PKC activity was reduced through prolonged incubation with PMA for 16 h, a significant reduction of monocyte adhesion on fibrinogen was observed. Peptides containing RGD sequences, which have been demonstrated to be ligands for certain integrins, did not inhibit monocyte adhesion. The data suggest that fibrinogen promotes monocyte adhesion in vitro by a PKC-dependent mechanism. PKC appears to be important not only for the initial cell adhesion but also for sustained binding of monocytes to fibrinogen.
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PMID:Fibrinogen promotes monocyte adhesion via a protein kinase C dependent mechanism. 884 67

Advanced glycation endproducts (AGEs) are derivatives of nonenzymatic reactions between sugars and protein or lipids, and together with AGE-specific receptors are involved in numerous pathogenic processes associated with aging and hyperglycemia. Two of the known AGE-binding proteins isolated from rat liver membranes, p60 and p90, have been partially sequenced. We now report that the N-terminal sequence of p60 exhibits 95% identity to OST-48, a 48-kDa member of the oligosaccharyltransferase complex found in microsomal membranes, while sequence analysis of p90 revealed 73% and 85% identity to the N-terminal and internal sequences, respectively, of human 80K-H, a 80- to 87-kDa protein substrate for protein kinase C. AGE-ligand and Western analyses of purified oligosaccharyltransferase complex, enriched rough endoplasmic reticulum, smooth endoplasmic reticulum, and plasma membranes from rat liver or RAW 264.7 macrophages yielded a single protein of approximately 50 kDa recognized by both anti-p60 and anti-OST-48 antibodies, and also exhibited AGE-specific binding. Immunoprecipitated OST-48 from rat rough endoplasmic reticulum fractions exhibited both AGE binding and immunoreactivity to an anti-p60 antibody. Immune IgG raised to recombinant OST-48 and 80K-H inhibited binding of AGE-bovine serum albumin to cell membranes in a dose-dependent manner. Immunostaining and flow cytometry demonstrated the surface expression of OST-48 and 80K-H on numerous cell types and tissues, including mononuclear, endothelial, renal, and brain neuronal and glial cells. We conclude that the AGE receptor components p60 and p90 are identical to OST-48, and 80K-H, respectively, and that they together contribute to the processing of AGEs from extra- and intracellular compartments and in the cellular responses associated with these pathogenic substances.
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PMID:Molecular identity and cellular distribution of advanced glycation endproduct receptors: relationship of p60 to OST-48 and p90 to 80K-H membrane proteins. 885 6

We determined the vascular and airway effects of PGF2 alpha and its mechanism of action on isolated-perfused lungs of rats were isolated and perfused at 50 ml/kg/min with Krebs-Henseleit bicarbonate buffer solution containing 3% bovine serum albumin. The lungs were ventilated with 21% O2 and 5% CO2 at a tidal volume of 2 ml. frequency of 60 per minute and positive end expiratory pressure of 3 cmH2O. Following injection of 50 micrograms PGF2 alpha into the afferent pulmonary catheter, there was a marked rise in pulmonary arterial pressure (Ppa) and in resistance to airflow across the lung (RL) and a fall in dynamic lung compliance (Cdyn). Double vascular occlusion technique revealed that 29% of the rise in Ppa was due to an increase in upstream and 71% to downstream resistance. N omega-nitro-L-arginine, 100 microns, a NO synthase inhibitor potentiated the Ppa response two-fold with significant change in airway mechanics. Rat atrial natriuretic factor (r-ANF), 40 micrograms quickly reversed the changes in Ppa, RL and Cdyn. Infusion of r-ANF prior to PGF2 alpha attenuated the Ppa response by 38%, RL by 44% and Cdyn by 12%. SQ 29548, a thromboxane receptor blocker and Cl, a protein kinase C (PKC) inhibitor, fully blocked both the vascular and airway responses to PGF2 alpha. PGF2 alpha is a constrictor of pulmonary vessels and airways in rat lungs via thromboxane SQ 29548 receptors, thansduced by intracellular PKC.
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PMID:PGF2 alpha causes bronchoconstriction and pulmonary vasoconstriction via thromboxane receptors in rat lung. 888 79

Endocytosis of fluorescently-labeled bovine serum albumin by digest cells of the gut of the cattle tick Boophilus microplus is inhibited by approx 60% in the presence of the tumour promoter 12-O-tetradecanoylphorbol 13-acetate. The results are consistent with a role for protein kinase C in regulating the uptake of blood meal by digest cells. Protein kinase C activity has been measured in the digest cell and the amount of enzyme has also been determined using a phorbol ester binding assay. The presence of a small number of specific protein kinase C substrates in the plasma membrane of the digest cell has been demonstrated. Preliminary experiments indicate that one of these substrates, a protein of approximately 30 kDa, is an integral membrane protein, part of which is exposed on the extracellular surface of the digest cell.
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PMID:Endocytosis by digest cells of the cattle tick Boophilus microplus: regulation by protein kinase C. 888 57

The objective of the present study was to examine the effect of modifying the fatty acid composition of membranes on cell growth and phosphoinositide specific phospholipase C (PLC) activity in HT-29 colon cancer cells. Cells were seeded at a density of 12 x 10(3) cells/cm2 and supplemented with 30 microM of either 18:0, 18:2 (n6) or 18:3 (n3) complexed to bovine serum albumin (BSA) in DMEM medium. Cell growth was followed for 12 days. The 18:0 supplemented cells (control) reached maximum growth at day nine which was greater than either 18:2 (n6) or 18:3 (n3) supplemented cells. There was no difference between the latter two groups in their growth. To investigate the fatty acid incorporation of the supplemented fatty acid and how they may influence composition in the cell membrane, we examined the fatty acid composition of each phospholipid (PL) species. Both phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were significantly influenced by the type of fatty acid supplemented. Supplementation with 18:0 resulted in HT-29 cell membranes having more monounsaturated fatty acids than the cells grown in the other fatty acids. Polyunsaturated fatty acid (PUFA) supplementation (both 18:2 and 18:3) resulted in the enrichment of PUFA in the PL fractions. Cells supplemented with 18:3 (n3) had the highest unsaturation index in membrane PE as compared to the other phospholipid species. PLC activity of the membranes was measured using PIP2 as a substrate in the presence of 15 micrograms alamethicin and 42 microM free calcium. The contribution of G protein to the activity of the enzyme was assessed using GTP gamma(S). PLC activity of HT-29 cells was 16% higher in the presence of GTP gamma(S) response. GTP gamma(S)-activated PLC activity of 18:3 (n3) supplemented cells was 81% of those supplemented with either 18:0 or 18:2 (n6) cells. It is concluded that the decrease in cell proliferation with supplementation with 18:3 (n3) may be mediated through its inhibitory effect on PLC, which provides the second messengers for protein kinase C (PKC) activation. PLC may be influenced by an increased unsaturation index of the PE fraction of the HT-29 tumor cell membranes.
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PMID:Effect of membrane lipid alteration on the growth, phospholipase C activity and G protein of HT-29 tumor cells. 898 25

The role of arachidonic acid was examined in the regulation of dopamine transport in C6 glioma cells stably expressing the human dopamine transporter. Exogenously added arachidonic acid (20-160 microM) stimulated [3H]dopamine uptake when pre-incubated for short times (15-30 min); 160 microM arachidonic acid inhibited following longer pre-exposures (45-60 min). Under the same conditions, only decreases were observed in the binding of the cocaine analog [3H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane ([3H]WIN 35,428). The reduction in dopamine transporter activity by arachidonic acid (at 160 microM for 60 min) was caused by a decrease in the Vmax (from 202 to 44 pmol/mg/min) opposed by a smaller reduction in K(m) (from 1.2 to 0.8 microM), whereas the effect of arachidonic acid (at 160 microM for 15 min) on [3H]WIN 35,428 binding was caused by a reduction in the Bmax (from 1.8 to 1.3 pmol/mg) without a change in Kd (7.2 nM). Upon 15-min exposure, melittin, an activator of phospholipase A2, and nordihydroguaiaretic acid, a lipooxygenase inhibitor, both expected to cause enhanced endogenous arachidonic acid, inhibited [3H]dopamine uptake and [3H]WIN 35,428 binding with an IC50 value close to 1 microM, whereas thimerosal, which raises arachidonic acid by inhibiting lipid reacylation, caused similar reductions at the sub-millimolar level. Co-presence of stauroporine (0.3-2 microM), an inhibitor of protein kinase C, had little or no effect on the melittin- or arachidonic acid-induced inhibition of [3H]dopamine uptake. Both the melittin- and arachidonic acid-, but not phorbol 12-myristate 13-acetate-induced inhibition of uptake were counteracted by bovine serum albumin (0.1 and 1 mg/ml) which binds arachidonic acid. The data taken together suggest that the inhibitory effects of arachidonic acid activators and those of protein kinase C activators on dopamine uptake are mediated by separate mechanisms.
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PMID:Regulation of the functional activity of the human dopamine transporter by the arachidonic acid pathway. 898 75

Stimulation of the IgE receptors on mast cells and basophils activates protein tyrosine kinases and phospholipases leading to histamine release. However, the mechanism by which protein tyrosine kinases regulate the phospholipases is not clearly defined yet. In this study, we examined the possibility that phospholipase C gamma 1 associates with protein tyrosine kinases and tyrosine phosphorylated molecules as a result of activation of RBL-2H3 cells, and that this association involves the Src homology 2 domains of phospholipase C gamma 1. An increase in cytoplasmic Ca2+ level and tyrosine phosphorylations of proteins, including 72 and 40 kDa proteins, were observed after the cross-linking of the IgE receptors on RBL-2H3 rat basophilic cells by dinitrophenyl-specific IgE and dinitrophenyl-conjugated human serum albumin. Immunoprecipitation and coprecipitation experiments were performed to determine if the activation of protein tyrosine kinases is linked to the activation of phospholipase C gamma 1 via its SH2 domains. Tyrosine phosphorylation of phospholipase C gamma 1 was observed in 1 min following IgE receptor stimulation. several proteins (72, 50, 40, and 33 kDa) were identified to be tyrosine phosphorylated and specifically associated with phospholipase C gamma 1 by its Src homology 2 domains. In addition, the coprecipitated complex contains the tyrosine kinase activity which phosphorylates 72, 40, and 33 kDa proteins in the complex. In conclusion, these studies establish that tyrosine-phosphorylated proteins of 72, 40, and 33 kDa associate with phospholipase C gamma 1 via its SH2 domains following IgE receptor stimulation of RBL-2H3 basophilic cells, implying that protein tyrosine kinases may tyrosine-phosphorylate and recruit signaling proteins around the phospholipase C gamma 1 and that phospholipase C gamma 1 activation induces calcium mobilization, PKC activation and degranulation in mast cells or basophils.
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PMID:Fc epsilon RI-ligation induces association of tyrosine phosphorylated proteins with Src homology 2 domains of phospholipase C gamma 1 in RBL-2H3 rat basophilic leukemia cells. 913 19

The cellular events following interaction between matrix proteins and cells are important requisites for physiological mechanisms as well as the progress of a number of diseases. Cellular adhesion to fibronectin, an important component of the extracellular matrix has been demonstrated to be associated with translocation of protein kinase C (PKC) by an integrin-dependent pathway. For this process G-proteins may play an important role as coupling proteins. Membrane association and activity of G-proteins has been shown to be regulated by isoprenylation. We therefore studied whether fibronectin mediated adhesion resulted in PKC translocation and if isoprenylation of cellular proteins may play a role for this integrin-dependent pathway of PKC activation. Chinese hamster ovary (CHO) cells were pretreated with either the Hydroxy-methylglutaryl(HMG)-CoA reductase inhibitor lovastatin or prenylation inhibitor limonene. For the stimulation by extracellular matrices, CHO cells were plated on tissue culture dishes coated with fibronectin or bovine serum albumin and PKC activity was determined. To investigate direct effects of inhibition of isoprenylation on cytoskeletal organization, phalloidin-stained stress fibers were characterized after adhesion on different matrices. CHO cells seeded on fibronectin displayed over twice the PKC translocation to the particulate fraction in comparison to that measured in cells on albumin. Pretreatment of CHO cells with lovastatin or limonene resulted in partial suppression of PKC activation after cell-seeding on the specific matrix fibronectin. Changed PKC distribution was not due to a disorganization of the actin skeleton. These data show that inhibition of isoprenylation of cellular proteins, possibly small Guanosine triphosphate(GTP)-binding proteins, alters only the integrin-mediated PKC distribution but does not greatly influence constitutive PKC distribution.
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PMID:Protein kinase C activation after cellular adhesion on fibronectin: partial suppression after inhibition of protein isoprenylation. 923 6

To investigate the involvement of protein kinases in signal transduction in the human zona pellucida (ZP)-induced acrosome reaction (AR), the effects of protein kinase (PK) activators, dibutyryl cAMP (PKA) and cGMP (PKG), phorbol 12-myristate 13-acetate (PMA, PKC), and the PKC inhibitor, staurosporine were studied. Sperm samples were obtained from normozoospermic men with normal sperm-ZP binding. Oocytes were obtained from other patients with failure of fertilization in vitro. Motile spermatozoa selected by a swim-up technique were pre-incubated with 2.5-20 microM PMA, 1 mM dibutyryl cAMP or cGMP, 3 mM pentoxifylline or 0.125-2.0 microM staurosporine for 30 min and then incubated with four oocytes for 2 h in human tubal fluid supplemented with bovine serum albumin. The spermatozoa bound to the ZP were dislodged by repeatedly aspirating the oocytes with a small bore pipette and the state of the AR was determined by fluorescein-labelled Pisum sativum agglutinin. Motility and movement characteristics were assessed by computer-assisted sperm analysis (CASA) after incubation of spermatozoa with PMA for 30 min and 2 h. The dibutyryl cAMP and cGMP analogues had a small positive effect (P < 0.05) but pentoxifylline had no effect on stimulating the ZP-induced AR (P > 0.05). In contrast, PMA stimulated ZP-induced AR in a marked dose-dependent manner. Only the highest concentrations (15-20 microM) of PMA significantly decreased percentage motility (P < 0.001). Doses of 2.5-15 microM of PMA significantly stimulated ZP-induced AR without decreasing motility (P < 0.001). The PKC inhibitor, staurosporine (0.125-0.25 microM) significantly inhibited ZP-induced AR without affecting motility (P < 0.001). Sperm samples from 33 normozoospermic men were used for studies of the ZP-induced AR augmented with 15 microM PMA. One sample did not show a response to PMA stimulation. Among the 14 men with low ZP-induced AR, half had normal responses to PMA and other half had low responses to PMA. In conclusion, activation or inhibition of PKC significantly increases or decreases human ZP-induced AR suggesting that PKC plays a important role in the signal transduction pathway for the physiological AR.
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PMID:Protein kinase C plays an important role in the human zona pellucida-induced acrosome reaction. 946 48

The effect of glucocorticoid(GC) on peak cytosolic free calcium net increment (delta[Ca2+]i) induced by high-K+ was detected with MiraCal Image System. The main results were as follows: (1) Corticosterone(B) could inhibit delta[Ca2+]i in a time-dependent and concentration-dependent manner. (2) The inhibitory effect of B could be mimicked by bovine-serum albumin conjugated corticosterone (B-BSA) also in a dose-dependent manner. (3) G-protein inhibitor, either PTX or GDP beta S significantly reduced the inhibitory effect of B and B-BSA on delta[Ca2+]i (4) PMA, a stimulator for protein kinase C(PKC), could inhibit delta[Ca2+]i. (5) Although the inhibitors of PKC, chelerythrine chloride and bisindolylamide I per se had no influence on delta[Ca2+]i, but they significantly antagonized the inhibitory effect of B and B-BSA on delta[Ca2+]i. It is postulated that GC inhibit delta[Ca2+]i induced by high-K+ through a membrane mechanism and by a pathway involving G-protein and PKC.
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PMID:The rapid inhibitory effect of glucocorticoid on cytosolic free Ca2+ increment induced by high extracellular K+ and its underlying mechanism in PC12 cells. 951 37


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