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)

We examined the effect of dibutyryl cAMP (dbcAMP) on the expression of LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18), and VLA-4 (CD49/CD29) and on eosinophilic differentiation of a human leukemia cell line, EoL-1. Dibutyryl cAMP induced eosinophilic differentiation of EoL-1 cells from 6-9 days after the start of culture with down-regulation of CD11a, CD18, and CD49 expression and up-regulation of CD11b expression. Changes in integrin expression, except for CD18, were seen predominantly in the fraction containing eosinophilic granule-positive cells, suggesting that the changes were dependent on eosinophilic differentiation. On the other hand, dbcAMP-induced changes of integrin expression were reversible and were not seen on day 9 when dbcAMP was removed on day 3, whereas eosinophilic differentiation was still present. A combination of G-CSF and TNF-alpha, which also induced eosinophilic differentiation of EoL-1 cells, increased CD11b expression slightly but had no significant effect on the expression of the other integrins. Butyrate and PMA up-regulated CD11b expression without eosinophilic differentiation. The results collectively suggest that the regulation of integrin expression on EoL-1 cells is partly dependent and partly not dependent on eosinophilic differentiation. The possible involvement of protein kinase A and protein kinase C in these changes is suggested.
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PMID:Effects of cyclic AMP on expression of LFA-1, Mac-1, and VLA-4 and eosinophilic differentiation of a human leukemia cell line, EoL-1. 752 82

The T cell surface molecules CD5 and CD28 have been shown to be receptors for accessory signals in T cell activation. We here demonstrate that in the absence of any other activating stimulus, simultaneous ligation of CD5 and CD28 by mAb induces polyclonal T cell activation. Immobilization of the anti-CD28 and anti-CD5 mAb was an essential requirement for T cell stimulation. This was done either through coating of the culture plates with goat anti-mouse Ig, or by coculture with mitomycin C-treated Fc gamma R-bearing P815 mouse mastocytoma cells. Most importantly, T cells could also be stimulated with B7, the natural ligand of CD28, and anti-CD5 presented on irradiated 3T6 mouse fibroblasts co-transfected with human Fc gamma RII and with B7. Neither immobilized mAb 9.3 (anti-CD28) nor any of four different anti-CD5 mAb were mitogenic as a sole stimulus. Immobilized mAb identifying CD4, CD7, or LFA-1 were not co-mitogenic with either mAb 9.3 or one of the anti-CD5 mAb. The T cell proliferation induced by cross-linking of CD5 and CD28 is IL-2-dependent, as was demonstrated by the cell-surface expression of the p55 chain of the IL-2R, the production of IL-2, and inhibition of the proliferative response by the anti-IL-2R mAb anti-Tac. CD5/CD28 ligation induced production of TNF-alpha, but not of IL-4, and did not induce modulation of the TCR/CD3 complex. Expression of IL-2R (p55) and of CD69 preferentially occurred on CD29-low naive cells, and indicated that about 50% of the cultured cells were activated. Cell proliferation was not increased by adding monocytes to the cultures and it was inhibited by PKC inhibitors (H7 and staurosporine) and by cyclosporine A. In conclusion, our data provide evidence for a pathway of Ag-independent T cell activation via CD5 and CD28, which preferentially stimulates native T cells.
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PMID:Simultaneous ligation of CD5 and CD28 on resting T lymphocytes induces T cell activation in the absence of T cell receptor/CD3 occupancy. 767 24

A twofold increase in lymphocyte adherence to rat microvascular endothelial cells (EC) was achieved by incubating EC for 4 h with IL-1 alpha or dibutyryl-cAMP (stimulators of protein kinase A, PKA) and PMA (stimulator of protein kinase C, PKC). Monoclonal antibodies anti-CD11a, anti-CD18 (LFA-1) and anti-CD49d (VLA-4 alpha) significantly inhibited the increased lymphocyte binding to IL-1 alpha-induced EC, anti-CD18 and to a lesser extent anti-CD11a and anti-CD49d to dibutyryl-cAMP-induced EC, whereas only anti-CD11a and anti-CD18 monoclonal antibodies inhibited PMA-induced lymphocyte binding. These findings suggest that stimulation of PKA and PKC induces lymphocyte binding to EC via different adhesion molecules.
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PMID:Adhesion molecules involved in protein kinase A- and C-dependent lymphocyte adherence to microvascular endothelial cells. 768 Jan 40

Through physiologic interactions with its ligands CD58 (lymphocyte function-associated Ag-3, LFA-3) and CD59, the T cell glycoprotein CD2 plays a role in T cell signaling and promotes lymphocyte adhesion. We have recently demonstrated that the interaction of CD2 with CD58 is dynamic: TCR stimulation or treatment with the phorbol ester PMA rapidly up-regulates CD2 ligand avidity, and this regulation requires the carboxyl-terminal asparagine residue of the CD2 cytoplasmic domain. Here we have analyzed the regulation of CD2 avidity for CD58, as assessed by the binding of CD2+ cells to purified CD58 and by the formation of rosettes between CD2+ cells and SRBC. In murine T cell hybridomas transfected with human CD2, we show that, unlike CD2-mediated IL-2 production, cell surface expression of the TCR-CD3 structure is not required for up-regulation of CD2 ligand avidity. TCR-initiated up-regulation of CD2 avidity requires the activity of both protein tyrosine kinases and protein kinase C. Agents which elevate intracellular levels of cAMP also up-regulate CD2 ligand avidity and act either distal to or independently of protein kinase C and protein tyrosine kinases. Cell lines expressing single amino acid substitutions of the carboxyl-terminal asparagine of CD2 are incapable of avidity regulation by TCR signaling, PMA treatment, or elevation of intracellular cAMP levels, demonstrating that each of these stimuli utilizes a common structural element for regulating CD2 avidity. The response to both cAMP and phorbol ester treatment distinguishes the regulation of CD2 avidity from that of a second major adhesion pathway, LFA-1 (CD11a/CD18)/ICAM-1 (CD54) and from that of the TCR coreceptor CD8. These observations identify the signaling events involved in the regulation of CD2 avidity and help to define the signal transduction processes that participate in "inside-out" signaling.
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PMID:Signal transduction pathways involved in T cell receptor-induced regulation of CD2 avidity for CD58. 768 Oct 75

The CD5 and CD28 molecules on T lymphocytes can each exert an accessory role in T-cell activation. Ligands for CD5 and CD28 have been identified as CD72 and B7/BB1 respectively. The function of, and the signal transduction pathways coupled to CD28 have been the subject of extensive studies. In contrast, it is still debated whether CD5 functions as a receptor which directly transduces an independent signal to the T cell. In this paper, it is reported that culture of purified T cells in the presence of either immobilized anti-CD5 monoclonal antibody (mAb) (OKT1, Leu-1 or 10.2) or cross-linked anti-CD28 (9.3) mAb (but not of anti-LFA-1 alpha, anti-LFA-1 beta, or anti-CD7) induces expression of CD69, an early activation marker, in the absence of other activating stimuli. CD69 expression was consistently detectable after 3-24 hr on 20-50% of T cells, within both the CD4 and CD8 subsets. CD45RO- CD45RA+ naive T cells were more responsive than CD45RO+ CD45RA- memory T cells. In the presence of recombinant (r) interleukin-2 (IL-2), anti-CD5- or anti-CD28- induced CD69 expression was further up-regulated, more sustained and, as previously shown, succeeded by IL-2 responsiveness. Simultaneous cross-linking of both CD5 and CD28 enhanced CD69 expression above the levels obtained with optimal amounts of both ligands separately. In the presence of a submitogenic dose of the protein kinase C (PKC) activating agent phorbol 12-myristate 13-acetate (PMA), co-stimulation with anti-CD5 or anti-CD28 increased CD69 expression above that induced by PMA alone. Cross-linking of CD5 or CD28 induces an early rise of cytoplasmic free calcium concentration ([Ca2+)]i) and both this rise and CD69 expression were inhibited by chelation of extracellular Ca2+ with ethyleneglycol-bis-(2-aminoethyl)-tetraacetate (EGTA). Pretreatment of the cells with the tyrosine kinase inhibitor herbimycin A also blocked CD69 expression. The data thus antigen-independent fashion. Moreover it is demonstrated that influx of Ca2+ and tyrosine kinase activity are involved in the signal transduction pathways of both receptors.
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PMID:Ligation of the CD5 or CD28 molecules on resting human T cells induces expression of the early activation antigen CD69 by a calcium- and tyrosine kinase-dependent mechanism. 768 35

We have raised a monoclonal antibody (mAb), NG2B12, directed against rat CD18, capable of inducing lymphocyte homotypic adhesion and granulocyte adherence to plastic. NG2B12-induced aggregation is temperature sensitive and requires metabolic energy, an intact cytoskeleton and the presence of Mg2+, but is independent of protein synthesis. Ca2+ is not only dispensable but exerts a suppressive effect on the NG2B12-induced adhesion. The adhesion is readily observed in thymocytes and concanavalin A blasts of thymocytes and splenocytes but is very weak in resting spleen and lymph node cells. NG2B12 also enhances phorbol 12-myristate 13-acetate (PMA)-induced aggregation in an additive fashion. The NG2B12-induced homotypic adhesion is mediated by LFA-1. mAb against ICAM-1 completely inhibited the induced adhesion of activated cells but inhibited only partially and in a time-dependent manner the adhesion of resting thymocytes. The activation of protein phosphatases 1 and 2A (as assessed by the use of okadaic acid) is necessary for the NG2B12-induced adhesion of both resting and activated thymocytes. In contrast, H-7 (an inhibitor of protein kinase C and A), substantially suppressed the adhesion of resting thymocytes, whereas W-7 (an inhibitor of calmodulin-dependent protein kinase) inhibited the adhesion of activated thymocytes. NG2B12 induces both adherence to plastic and homotypic aggregation of granulocytes; the events being blocked by anti-CD18 (WT.3) and anti-CD11b/CD11c (OX-42) mAb, augmented by okadaic acid and not modified by H-7 and W-7. Additionally, we have demonstrated that NG2B12 and PMA employ distinct intracellular signaling pathways in inducing adhesion of both thymocytes and granulocytes.
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PMID:A novel anti-rat CD18 monoclonal antibody triggers lymphocyte homotypic aggregation and granulocyte adhesion to plastic: different intracellular signaling pathways in resting versus activated thymocytes. 791 39

CD2, CD3, and MHC class II have been demonstrated to stimulate lymphocyte function-associated antigen (LFA)-1 (CD11a/CD18) mediated adhesion (Van Kooyk et al., 1989, Dustin and Springer, 1989; Mourad et al., 1990). Activation of LFA-1 may be mediated by different intracellular signals generated from these stimuli, since previous findings suggest that triggering of LFA-1 through CD2 or CD3 leads to sustained and transient cell adhesion respectively (Van Kooyk et al., 1989). We investigated the role of intracellular signalling pathways in more detail. The results demonstrate that, in addition to protein tyrosine kinase (PTK) and protein kinase C (PKC) mediated signalling, increase in cytosolic-free calcium ([Ca2+]i) levels play a major role in the activation of LFA-1. The calcium ionophore Ionomycin, which increases [Ca2+]i is capable of directly activating LFA-1. Furthermore, activation of LFA-1 by triggering through CD2, CD3 or MHC class II is associated with an increase in [Ca2+]i levels, with kinetics that directly correlate with cell adhesiveness. Moreover, entry of extracellular Ca2+ via Ca-channels is involved in both the CD3- and MHC class II, as well as part of the CD2 induced LFA-1 activation. Depletion of intracellular calcium results in unresponsiveness of LFA-1 to these stimuli, further demonstrating a regulatory role for [Ca2+]i in LFA-1 mediated adhesion.
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PMID:Role of intracellular Ca2+ levels in the regulation of CD11a/CD18 mediated cell adhesion. 791 56

Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a widely distributed cell adhesion molecule present on monocytes, macrophages, and monocytic cell lines. Treatment of the promonocytic cell line U-937 with TGF-beta 1 induces homotypic cellular aggregations, simultaneous with an increase in surface expression and specific transcripts of PECAM-1. The TGF-beta-induced cell adhesion phenomena are not dependent on LFA-1, intercellular adhesion molecule-1 (ICAM-1), very late Ag-4 (VLA-4), or very late Ag-5 (VLA-5). However, the phenomena seem to be directly mediated by PECAM-1 because 1) it is inhibited by the addition of Abs or an antisense oligonucleotide specific for PECAM-1; and 2) TGF-beta 1-treated U-937 cells bind to PECAM-1-expressing mouse transfectant fibroblasts, but not to mock transfectants. In addition, this aggregation phenomena are divalent cation-dependent and requires the integrity of the cytoskeleton. Analysis of the intracellular signaling pathways indicates that TGF-beta 1 induces protein kinase C activity, as well as PECAM-1 phosphorylation and association with cytoskeletal components. Furthermore, in this model, an autocrine mechanism for releasing the bioactive form of TGF-beta 1 operates, allowing PECAM-1 activation. These results provide evidence that TGF-beta 1 regulates PECAM-1 function by increasing the expression and activating the adhesion of PECAM-1 in monocytic cells. These two mechanisms seem to be necessary for adhesion because independent inhibition of either expression or activation of PECAM-1 leads to abrogation of cellular aggregation.
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PMID:Functional regulation of platelet/endothelial cell adhesion molecule-1 by TGF-beta 1 in promonocytic U-937 cells. 793 Jun 23

The T cell surface molecule CD28 binds to ligands on accessory cells and APCs, playing an important costimulatory role in the response of T cells to Ags. Our knowledge of the intracellular signaling pathways coupled to this receptor is incomplete. In addition to activation of phospholipase C gamma 1, ligation of this receptor also seems to activate a calcium-independent, CD28-specific pathway. In this paper, we report that cross-linking of CD28 (but not CD2, CD5, LFA-1, or CD7) leads to an elevation of c-jun mRNA, with only minimal activation of c-fos expression. CD28-dependent induction of c-jun expression requires protein tyrosine kinase activity, but does not depend on activation of a phorbol ester-responsive protein kinase C or elevation of cytosolic calcium. Furthermore, CD28-dependent elevation of c-jun mRNA does not appear to be mediated at the level of mRNA stability. A mechanism is suggested whereby expression of c-jun and junB, in the absence of members of the fos family, can prevent inappropriate activation of T cells caused by ligation of CD28 in the absence of a specific antigenic stimulus.
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PMID:Differential regulation of proto-oncogenes c-jun and c-fos in T lymphocytes activated through CD28. 798 45

Changes in adhesive properties play important regulatory roles in activation and differentiation of B-cells. To better understand the regulation of interactions between B-cells and other cells during the immune response, we have studied surface expression of the adhesion molecules LFA-1 (CD11a/CD18) and ICAM-1 (CD54). Both adhesion molecules were upregulated during B-cell activation. However, upon stimulation with anti-IgM and IL-4, ICAM-1 levels started to increase within 12 hr, while LFA-1 levels did not start to increase until after 36 hr. When B-cells were stimulated with the PKC activator PDB and a calcium ionophore, ICAM-1 levels, but not LFA-1 levels, increased. Only if these activators were removed after around 24 hr of activation and the cells were recultured in fresh medium was there an eightfold induction of LFA-1. Such reculturing in fresh medium led, however, to decreased ICAM-1 levels.
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PMID:Differential regulation of LFA-1 and ICAM-1 on human primary B-lymphocytes. 809 39


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