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

Functional studies were performed on human peripheral blood T lymphocytes stained with goat anti-5'-nucleotidase antibodies and separated into ecto-5'-nucleotidase (ecto-5'-NT)-positive and -negative populations using the FACSTAR fluorescence-activated cell sorter. On the average, ecto-5'-NT+ T cells contained 34 +/- 13% CD4+ and 55 +/- 15% CD8+ cells, whereas ecto-5'-NT-T cells contained 65 +/- 12% CD4+ and 23 +/- 8% CD8+ cells. Staining with anti-5'-NT antibodies did not significantly alter the ability of unseparated T cells to proliferate in response to PHA or PMA, or in a MLR. However, prior incubation with anti-5'-NT antibodies did inhibit the ability of irradiated T cells to provide help for PWM-stimulated Ig synthesis by as much as 55%. In five separate experiments, ecto-5'-NT-T cells demonstrated an equal or better ability to incorporate [3H]TdR after PHA stimulation or in a MLR, as compared with ecto-5'-NT+ T cells. Similarly, ecto-5'-NT- T cells were not diminished in their ability to provide help for autologous B cells in a PWM-driven system. Clearly, the inability of ecto-5'-NT- T cells from patients with a variety of immunodeficiency diseases to function in these assays cannot be explained solely by their lack of ecto-5'-NT activity. In contrast, ecto-5'-NT-positive and -negative T cells showed markedly different dose-response curves for proliferation in response to PMA. Ecto-5'-NT+ T cells responded to lower doses of PMA (1.0 ng/ml) than did ecto-5'-NT- T cells and showed a two- to eight-fold greater rate of [3H]TdR incorporation at 3 to 10 ng of PMA per ml. Ecto-5'-NT+ T cells may have a protein kinase C that is more accessible or more easily activated or may utilize an alternate pathway of activation when stimulated with low concentrations of PMA.
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PMID:Functional characterization of ecto-5'-nucleotidase-positive and -negative human T lymphocytes. 253 56

Activation of Jurkat T lymphocytes to produce IL2 is accompanied by a strong inhibition of phosphatidylserine (PS) synthesis. This inhibition was obtained either with the mitogenic lectin PHA, anti-CD3 monoclonal antibodies (mAb), anti-CD2 mAb or anti-Ti mAb. Bypassing membrane receptor signalling, by using a Ca2+ ionophore or a protein phosphatase inhibitor, sodium ortho-vanadate, also results in a marked inhibition of PS synthesis. Activators of phospholipid -Ca2+ dependent protein kinase C (PKC) did not significantly modify PS synthesis, suggesting that the observed changes only involve the transduction of the first activation signal. PS being a necessary cofactor for PKC, our results strongly suggest that the inhibition of PS synthesis induced by receptor triggering exerts a feed back control on PKC therefore leading to a transient activation of the enzyme upon full lymphocyte activation.
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PMID:Phospholipid metabolism and T cell activation: receptor triggering is associated with the inhibition of phosphatidylserine synthesis. 257 21

Resting human T lymphocytes do not express receptors for interleukin-2, but expression is rapidly induced by exposure to PHA. After maximal expression 2-3 days after stimulation, a progressive decline in receptor number is observed. Receptor expression can be augmented by reexposure to PHA. In this study we show that activators of protein kinase C including phorbol diester, phospholipase C, and the diacylglycerol congener diC8 also increase IL-2 receptor expression. Moreover, 5-azacytidine, which inhibits cytosine methyltransferase, and hydroxyurea, which inhibits ribonucleotide reductase, also increased receptor number. These studies demonstrate that IL-2 receptor expression can be altered in vitro, and that IL-2 receptor number, in combination with IL-2 secretion, may contribute to the regulation of IL-2-dependent immune responses.
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PMID:Activators of protein kinase C and 5-azacytidine induce IL-2 receptor expression on human T lymphocytes. 258 Aug 52

Previous studies have shown that MAb's against the gangliosides GD3 and GD2 may augment T cell responses to a variety of stimuli. We present evidence that antiganglioside MAb's, like PHA, increase intracellular cGMP and protein kinase C yet have no effect on intracellular Ca2+. Stimulation of T cells with MAb's to GD3 was associated with increased cGMP levels, particularly in the CD8+ T cell subset which showed the highest degree of potentiation by the MAb's. Augmentation of T cell responses by the MAb's to GD3 and GD2 was also mimicked by activation of PKC with phorbol esters but both agents together produced marked synergistic effects on cell division, suggesting they had different but complementary modes of action. Furthermore, use of neomycin to inhibit PKC activation only partially reversed the augmentation of proliferative responses by the antiganglioside MAb's. It did however inhibit the MAb-induced increase in IL2 production and IL2 receptor (Tac) expression. These studies suggest therefore that the potentiation of IL2 production by the MAb's against GD2 and GD3 was due to enhanced activation of PKC whereas their augmentation of proliferative responses appeared to be due to effects on late events in T cell activation and was associated with both increased cGMP levels and activation of PKC.
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PMID:Augmentation of lymphocyte responses by monoclonal antibodies to the gangliosides GD3 and GD2: the role of protein kinase C, cyclic nucleotides, and intracellular calcium. 278 17

We have recently reported on the effect of PGE2 on T cell activation and suggested that their immunosuppressive effect may involve the PKC activation pathway. In the present study, we further investigated the potential interference of PGE2 with PHA induced signaling in T lymphocytes. We demonstrate that the PHA mediated increase in IP3, the putative mobilizer of intracellular Ca2+, is slightly affected following cell incubation with PGE2. Treatment of cell culture with the tumor promoter TPA abrogates the suppressive activity of PGE2 whereas exogenous diacylglycerol (1,2-diolein) has only a marginal effect. This suggests that PGE2 affect PKC activity at sites distal to IP3 and DG generation. We also demonstrate that the PGE2 suppressive effect on T lymphocyte activation is not related to an inhibition of PKC translocation.
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PMID:The inhibitory effect of PGE2 on T cell activation is not associated with inhibition of PKC translocation. 278 52

Activation of Jurkat T cells with anti-TCR, anti-CD3, anti-CD2, or PHA is accompanied by a strong inhibition of phosphatidylserine (PS) synthesis. The inhibition of the synthesis of this phospholipid could be partially reversed by IL-1. In Jurkat cells, IL-1 did not activate phosphodiesterases as demonstrated by the lack of change of inositol triphosphate and diacylglycerol levels as well as the lack of change in cytosolic Ca2+ concentration. Furthermore, IL-1 did not modify the intracellular level of cGMP and cAMP, suggesting that the observed rise of PS synthesis could play the role of mediator IL-1 action. As PS is a necessary cofactor for the activation of protein kinase C, our results suggest strongly that IL-1 modulate protein kinase C activity in the activated lymphocyte through its action on PS synthesis.
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PMID:IL-1 signaling for IL-2 production in T cells involves a rise in phosphatidylserine synthesis. 284 6

We have studied the suppressive ability of human cord blood lymphoid cells in a three-days mixed lymphocyte culture proliferation assay stimulated by mitogen. Sex chromosomes served as markers for dividing cord (male) or maternal cells. Three distinct mitogenic agents were used in the co-cultures: the mitogenic lectin PHA, the anti-CD3 monoclonal antibody OKT3, and 12-0-tetradecanoyl-13-acetate (TPA), a direct activator of protein kinase C. With all mitogens we observed significant, non-specific suppression of maternal/adult cell division. However, three separate levels of suppression were evident. PHA-stimulated co-cultures always showed the highest amount of cold suppressor activity (mean +/- SEM: 64.9 +/- 3.9). The mean suppression in OKT3- and TPA-stimulated co-cultures was 34.7 +/- 6.0 and 22.0 +/- 4.1%, respectively. Furthermore, indomethacin, a prostaglandin (PG) synthetase inhibitor, reduced by 41% the suppression in PHA-driven co-cultures, whereas having no significant effect on the corresponding OKT3-driven co-cultures. Our results indicate the existence of an indomethacine-sensitive, PG-dependent mechanism and a separate, indomethacine-resistant, mechanism of cord cell suppression.
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PMID:Distinct mitogens reveal different mechanisms of suppressor activity in human cord blood. 297 39

The addition of IL 2 to Con A-activated splenic T cells induced the rapid and time-dependent phosphorylation of membrane proteins with m.w. of 115,000 to 105,000, 90,000, and 66,000, and to a lesser extent 55,000 to 58,000, 40,000, and 34,000. Immunoprecipitations conducted with an anti-IL 2 receptor antibody indicated that the murine IL 2 receptor (55,000 to 58,000) was included in the set of IL 2-dependent phosphoproteins. Phosphorylation of these same proteins was also seen after IL 2 treatment of PHA-activated T cells and of the IL 2-dependent line CTLL-2. Membrane phosphorylation was dependent on physiologically relevant IL 2 concentrations (0.2 to 1 ng/ml), and was detected as early as 1 min after IL 2 addition, with maximal levels of phosphorylation achieved by 15 min. In contrast to these observations, the pattern of cytoplasmic protein phosphorylation remained unchanged after IL 2 addition, although IL 2 did augment the level of preexisting cytoplasmic phosphorylation induced by lectin. The pattern of membrane protein phosphorylation induced by IL 2 also overlapped in part with that induced after stimulation of Con A-activated T cells with the phorbol ester PMA. IL 2-stimulated phosphorylation was inhibited by the addition of agents that both stimulate cyclic AMP-dependent protein kinases and block lymphocyte mitogenesis. No effect was seen upon addition of agents that enhance cyclic GMP-dependent protein kinases. These observations support a role for specific membrane as opposed to cytoplasmic protein phosphorylation in the regulation of lymphocyte growth by IL 2, and also suggest that protein kinase A, and perhaps protein kinase C, participate as regulators of the IL 2 signaling mechanism.
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PMID:Interleukin 2-dependent phosphorylation of interleukin 2 receptors and other T cell membrane proteins. 300 13

The accumulation of cyclic AMP in Jurkat cells was stimulated by adenosine and adenosine analogues. The accumulation of cyclic AMP induced by these agents was competitively antagonized by the adenosine receptor antagonist 8-p-sulphophenyl-theophylline (KD appr 1.9 microM). The lectin PHA, the diacylglycerol OAG as well as tumor promoting phorbol esters enhanced the accumulation of cyclic AMP induced by the adenosine analogue NECA. The results suggest that activation of CD2/CD3 receptors by lectins could potentiate the endogenous cyclic AMP stimulator adenosine via activation of protein kinase C.
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PMID:The adenosine receptor mediated accumulation of cyclic AMP in Jurkat cells is enhanced by a lectin and by phorbol esters. 303 23

A B cell-specific monoclonal antibody (anti-Ba) was prepared. In two-color FACS analysis the anti-Ba reacted with a subpopulation of Ig+ or B1+ cells obtained from tonsils, but did not react with most B1+ cells derived from PBL. Activation of B cells from PBL with TPA or anti-mu induced Ba expression and the addition of PHA-conditioned supernatant with anti-mu-enhanced Ba expression. Other B cell activators, such as Staphylococcus aureus Cowan I (Staph-A) or PWM plus T cells, could induce Ba expression. Ba expression was observed 6 hr after stimulation and reached a peak level at 72 hr. Ba expression was strictly restricted to B cells. H-7, a specific inhibitor of protein kinase C (C-kinase), displayed a dose-dependent inhibitory effect on Ba expression, showing dependency on C-kinase for Ba expression. Anti-Ba inhibited B cell proliferation induced by anti-mu and B-BCGF distinct from BSF-1. The results presented in this study suggest that the Ba antigen on B cells may be comparable to the Tac antigen on T cells.
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PMID:Expression and function of an early activation marker restricted to human B cells. 308 51


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