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:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IFN-gamma secretion by Th1 cells has been shown to preferentially promote the production of IgG2a in LPS-stimulated murine B lymphocytes. We recently reported that PGE2 potentiated the ability of IFN-gamma to augment IgG2a production in both Ag-specific and polyclonal systems via a cAMP-dependent pathway. Because antibodies (Ab) directed against class II MHC molecules have been shown to induce a rise in B cell cAMP, we hypothesized that this event, like PGE2 treatment, would promote the production of IgG2a. In this manuscript, cultures of small and large B cells treated with anti-Ia Ab are shown to produce significantly higher levels of IgG2a, compared with cultures treated only with IFN-gamma and LPS. Moreover, the combined treatment of B lymphocytes with IFN-gamma and PGE2 followed by anti-Ia and LPS resulted in a fourfold rise in IgG2a levels compared with IFN-gamma and LPS. Only anti-class II, but not anti-class I Ab, stimulated IgG2a production. Utilizing an ELISA spot assay, the frequency of IgG2a-secreting B cells was determined to be elevated fourfold in anti-Ia treated B cells. B cell cultures incubated with either PGE2 or anti-Ia exhibited elevated levels of cAMP and treatment with IFN-gamma primed these lymphocytes to the cAMP-elevating effects of either PGE2 or anti-Ia. Finally, RpcAMP, a cAMP antagonist that blocks cAMP from activating protein kinase A, prevented the increased production of IgG2a induced by anti-Ia Ab. These results support the theory that a cAMP pathway exists that promotes B cell IgG2a production. Within this pathway, IFN-gamma sensitizes B lymphocytes to cAMP elevators such as anti-class II Ab, and in conjunction with LPS, causes an increase in the frequency of IgG2a-secreting cells and the amount of IgG2a produced. These observations suggest that, after exposure to viral Ag in vivo, interaction between IFN-gamma-primed murine B cells and T cells will potentiate production of IgG2a, the predominant murine anti-viral Ig.
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PMID:Anti-class II antibodies potentiate IgG2a production by lipopolysaccharide-stimulated B lymphocytes treated with prostaglandin E2 and IFN-gamma. 131 36

Ag independent adhesion between lymphocytes and target cells is mediated in part by the interaction between lymphocyte function associated Ag-1 (LFA-1) and its coreceptor intercellular adhesion molecule-1 (ICAM-1). Within minutes, PMA treatment of JY cells, which express both LFA-1 and ICAM-1, induced capping of LFA-1 and augmentation of intercellular adhesion lasting for several hours. However, over the course of 15 to 30 min, both of these events were blocked by elevation of intracellular cAMP concentration ([cAMP]i) presumably via activation of protein kinase A. This short term inhibition of protein kinase C-induced adhesion was in contrast to the long term augmentation of adhesion caused by increased [cAMP]i as demonstrated in the companion article. Intercellular adhesion, due to LFA-1/ICAM-1 interactions, could also be induced by LPS treatment of JY cells. At submaximal concentrations, the extent of aggregation induced by LPS had two maxima, one at 30 to 60 min and the other with a plateau at 5 to 8 h. LPS is known to activate protein kinase C and we show that LPS treatment induced increased [cAMP]i. Using inhibitors of protein kinases C and A, possible mediators of the two components of adhesion induced by LPS could be identified. The early component was abrogated by inhibition of protein kinase C although the later component was unaffected. In contrast, an inhibitor of protein kinase A had no affect on the early component and attenuated, but did not entirely eliminate, the late component. These results suggest a model of sequential induction, inhibition, and reinduction of LFA-1/ICAM-1-mediated lymphocyte adhesion that is regulated by temporally ordered actions and interactions of protein kinases C and A.
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PMID:Lymphocyte adhesion mediated by lymphocyte function-associated antigen-1. II. Interaction between phorbol ester- and cAMP-sensitive pathways. 135 28

Monocyte influx and activation in synovial joints are important in the pathogenesis of both degenerative and inflammatory arthropathies. In this study, we demonstrate the potential of articular cartilage to directly modulate these events. IL-1-stimulated human articular chondrocytes transcribed 0.7-kb monocyte chemoattractant protein-1 (MCP-1) mRNA. In situ hybridization of cartilage organ cultures revealed MCP-1 transcripts in chondrocytes in the superficial tangential zone within 2 h of stimulation with IL-1. Chondrocytes in deeper layers responded by 4 h and reached maximum MCP-1 mRNA levels by 8-12 h. IL-1-stimulated cartilage organ and chondrocyte monolayer cultures released functional monocyte chemotactic activity. This was neutralized by a monoclonal antibody specific for MCP-1, and was associated with the synthesis and secretion of immunoreactive 13-kD and 15-kD isoforms of MCP-1. Regulators and signal transduction pathways involved with the expression of the MCP-1 gene in chondrocytes were analyzed. Steady-state mRNA levels were increased by the known chondrocyte activators IL-1, tumor necrosis factor alpha, LPS, platelet-derived growth factor, and transforming growth factor beta. In addition, leukemia inhibitory factor induced MCP-1 gene expression and protein synthesis, identifying this cytokine as a new regulator of chondrocyte function. Dexamethasone blunted the induction of MCP-1 gene expression by IL-1 and by activators of protein kinase A as well as protein kinase C signal transduction pathways. In contrast, retinoic acid strongly increased phorbol myristate acetate-induced MCP-1 expression and potentiated the effects of IL-1 and LPS. In conclusion, chondrocytes express MCP-1 in response to factors that are present in cartilage or synovium. This provides a mechanism by which cartilage can play an active role in the initiation and progression of arthritis.
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PMID:Monocyte chemoattractant protein-1 (MCP-1) expression in human articular cartilage. Induction by peptide regulatory factors and differential effects of dexamethasone and retinoic acid. 136 41

Synthesis of complement proteins and their regulation in resident cells of the central nervous system are important pathophysiologic factors that can affect the outcome of inflammatory central nervous system diseases. Primary cultures of rat astrocytes constitutively express C3 mRNA and produce C3 protein; both of them were enhanced by LPS or by a live as well as inactivated Newcastle disease virus, a neurotropic paramixovirus. TNF, IL-1 beta, and IL-8 also increased the levels of C3 mRNA and protein whereas IL-1 alpha and IL-6 had no effect, although all of these cytokines are inducible by LPS. LPS stimulation in the presence of cycloheximide decreased the LPS-mediated C3 mRNA induction by 60%. These data suggest that LPS effect on C3 regulation is mediated directly by LPS as well as by LPS-induced cytokines. Interestingly, C3 mRNA induced by Newcastle disease virus or inactivated Newcastle disease virus was inhibited by protein kinase inhibitors, H-7 and staurosporine, whereas these inhibitors had no effect on C3 induction mediated by LPS or cytokines, indicating the existence of different signal transduction pathways.
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PMID:Induction of C3 expression in astrocytes is regulated by cytokines and Newcastle disease virus. 153 Sep 57

We have previously demonstrated that activation of protein kinase C (PKC) by phorbol esters induces selectively IgA synthesis by mouse B cells. In this study, we investigated the effects of a number of protein kinase inhibitors on IgA secretion induced by a recombinant murine IL-5 in LPS-stimulated mouse B cells. The results show that PKC inhibitors, such as sphingosine (SPH), staurosporine (STP) and H-7, blocked IL-5-induced IgA synthesis; the protein kinase A inhibitor HA-1004 and the inhibitor of calcium/calmodulin dependent protein kinase W-7 had no effect on IgA secretion induced by IL-5. The proliferation of the IL-5 sensitive B13 cell line in response to IL-5 was also inhibited by addition of SPH or STP or H-7. The data suggest an involvement of the PKC pathway in IL-5-induced B cell differentiation into IgA secreting cells.
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PMID:IL-5-induced IgA synthesis by LPS-stimulated mouse B cells is prevented by protein kinase C inhibitors. 158 1

In the first report in this series we described the relationships and evolution of 152 individual proteins of the EF-hand subfamilies. Here we add 66 additional proteins and define eight (CDC, TPNV, CLNB, LPS, DGK, 1F8, VIS, TCBP) new subfamilies and seven (CAL, SQUD, CDPK, EFH5, TPP, LAV, CRGP) new unique proteins, which we assume represent new subfamilies. The main focus of this study is the classification of individual EF-hand domains. Five subfamilies--calmodulin, troponin C, essential light chain, regulatory light chain, CDC31/caltractin--and three uniques--call, squidulin, and calcium-dependent protein kinase--are congruent in that all evolved from a common four-domain precursor. In contrast calpain and sarcoplasmic calcium-binding protein (SARC) each evolved from its own one-domain precursor. The remaining 19 subfamilies and uniques appear to have evolved by translocation and splicing of genes encoding the EF-hand domains that were precursors to the congruent eight and to calpain and to SARC. The rates of evolution of the EF-hand domains are slower following formation of the subfamilies and establishment of their functions. Subfamilies are not readily classified by patterns of calcium coordination, interdomain linker stability, and glycine and proline distribution. There are many homoplasies indicating that similar variants of the EF-hand evolved by independent pathways.
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PMID:Evolution of EF-hand calcium-modulated proteins. II. Domains of several subfamilies have diverse evolutionary histories. 160 95

This study analyzes the expression of monocyte chemoattractant protein-1 (MCP-1) by inflamed synovial tissue and defines its regulation in cultured synoviocytes. Synoviocytes from patients with rheumatoid arthritis and osteoarthritis express the 0.7-kb MCP-1 mRNA. Stimulation of synoviocytes with IL-1, TNF-alpha, LPS, platelet-derived growth factor, and transforming growth factor-beta-1, but not with basic fibroblast growth factor causes a marked increase in MCP-1 mRNA levels. Expression of the MCP-1 gene is inducible by activators of the protein kinase A (cAMP) and C (PMA) signal transduction pathways and is differentially regulated by the steroids dexamethasone and retinoic acid. Cultured synoviocytes de novo synthesize 12-, 15-, and 15.2-kDa MCP-1 proteins, which increase after stimulation with IL-1. Synovial tissues from donors without joint disease and from patients with rheumatoid or osteoarthritis were analyzed for MCP-1 mRNA expression by in situ hybridization. In these samples MCP-1 mRNA expressing cells were predominantly found in the sublining cell layers, whereas specimens of normal synovial tissue contained only few positive cells. These results identify synoviocytes as a source of MCP-1. Its expression is controlled by peptide regulatory factors that are known to be present in arthritic joints. Detection of cells producing MCP-1 mRNA in synovial tissues from patients with arthritis shows that this gene is expressed in vivo and suggests that MCP-1 can play a role in recruiting monocytes in joint inflammation.
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PMID:Production of monocyte chemoattractant protein-1 by inflamed synovial tissue and cultured synoviocytes. 162 9

Nuclear factor kappa-B (NF-kappa B) has been shown to play an important role in LPS-mediated induction of several genes in macrophages. Several studies have implicated protein kinase C (PKC) or cAMP-dependent protein kinase in the regulation of NF-kappa B activity. In this study we have investigated the mechanism of NF-kappa B induction in murine macrophages. A chloramphenicol acetyl transferase (CAT) expression vector containing multiple copies of the TNF-alpha NF-kappa B element was transfected into the RAW264 macrophage-like cell line and assessed for inducible CAT activity. LPS treatment of the transfected cells resulted in a significant induction of CAT activity. CAT activity was not induced by treatment with phorbol myristate acetate (PMA) or the cAMP analogue 8-bromo cAMP. To further study NF-kappa B induction, nuclear extracts were prepared from RAW264 cells. Extracts from RAW264 cells that were treated from 30 min to 2 hr with LPS had a significant increase in NF-kappa B binding activity as determined by the electrophoresis mobility shift assay (EMSA). Treatment of these cells from 30 min to 2 hr with PMA did not result in such binding activity. U.V. crosslinking analysis of the DNA-binding activity confirmed these results and indicated that LPS induced a 55 KD DNA-binding protein. Induction of this NF-kappa B binding activity was not inhibited by pretreatment with the PKC inhibitor H-7. H-7 did inhibit induction of TPA responsive element binding by either LPS or PMA. Prolonged exposure to phorbol ester, a treatment which down-regulates PKC, had no effect on LPS induction of NF-kappa B activity in these cells. These results suggest that the induction of NF-kappa B in macrophages by LPS is independent of PKC.
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PMID:Regulation of NF-kappa B activity in murine macrophages: effect of bacterial lipopolysaccharide and phorbol ester. 173 Jul 83

A single i.p. injection of cisplatin (10 mg/kg body weight) into mice results in a significant increase in chemiluminescence and ATP contents of the peritoneal exudate cells (PEC) than that of PEC from untreated mice. It is also observed that in vitro treatment of macrophages with cisplatin, rIFN-gamma and LPS show increased activity of the protein kinase-C (PK-C). The activation of PK-C could result in stimulation of NADPH-oxidase resulting in increased levels of chemiluminescence. Increased contents of ATP in PEC after cisplatin treatment also suggests that this activation is energy dependent.
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PMID:Studies on chemiluminescence and protein kinase-C activity of cisplatin treated mouse peritoneal exudate cells. 177 Feb 12

A potential role of protein kinase C (PKC) in lipopolysaccharide- (LPS-) induced tumoricidal activation of macrophages was investigated by using two mouse macrophage cell lines (P388D1 and J774). J774 cells are stimulated by LPS to kill target P815 mastocytoma cells, whereas P388D1 cells fail to develop such an ability. Pretreatment of J774 cells with H-7 or phorbol myristate acetate resulted in a significant inhibition of LPS-induced cytotoxicity, whereas pretreatment with H-8, ML-7, HA1004, or W-7 did not. Since these results suggested a critical role of PKC in the activation process, the properties of PKC in the two cell lines were compared. Western blotting with rabbit antiserum specific for the PKC beta regulatory domain allowed detection of a protein of 79 kilodaltons (kDa) in the detergent lysates of both cell lines that were not stimulated by LPS. However, LPS treatment resulted in the appearance of a second protein of 40 kDa only in J774 cells and not in P388D1 cells. Furthermore, two forms of protein kinase (one basic and the other acidic) were identified in the cytosol of J774 cells by HPLC on DEAE-5PW, whereas only the basic form was found in P388D1 cells. On the basis of the response of the basic and acidic form protein kinases to phosphatidylserine (PS), diolein, and Ca2+, the basic form was found to contain both regulatory and catalytic domains of PKC, whereas the acidic form was suggested to represent the PKC catalytic domain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein kinase C in tumoricidal activation of mouse macrophage cell lines. 190 55


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