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 long terminal repeat (LTR) of a retrovirus contains sequence elements that constitute a promoter for controlling viral gene expression in infected cells. We have examined regulation of LTR-directed gene expression in feline immunodeficiency virus (FIV), a T-lymphocytopathic lentivirus associated with a fatal AIDS-like disease in domestic cats. Two independent virus isolates, designated FIV-Petaluma and FIV-PPR, have been molecularly cloned and show greater than 85% sequence homology. Both clones (termed pF34 and pPPR) produce infectious virus after transfection of permissive feline cells. Basal promoter activity of the LTRs was measured in various cell lines in transient expression assays using plasmids containing the viral LTR linked to the bacterial chloramphenicol acetyltransferase gene. Both LTRs were strong promoters in several cell lines, although in some cell lines the pF34 LTR had four- to fivefold higher basal activity than the pPPR LTR. FIV LTR mutations affecting the first AP4 site, AP1 site, ATF site, or NF-kappa B site resulted in decreased basal activity of the FIV promoter. Mutational analysis also revealed a negative regulatory element. In cotransfection experiments, both pF34 proviral DNA and pPPR proviral DNA appeared to transactivate either the pF34 LTR or the pPPR LTR; however, levels of transactivation were very low. Cotransfection of both LTRs with FIV subgenomic clones containing various viral open reading frames resulted in low level or no transactivation. The LTRs of both FIV clones responded to cell activation signals in human T-lymphoid cells (Jurkat) treated with phytohemagglutinin and phorbol-12-myristate-13-acetate. Promoter function of both FIV LTRs was also enhanced in cells treated with either forskolin, an inducer of intracellular cyclic-AMP (c-AMP), or dibutyryl c-AMP. Analysis of site-specific mutants showed that a potential AP1 site in the U3 domain of the LTR was required for T-cell activation responses mediated by protein kinase C, whereas a putative ATF site was the target for c-AMP-induced responses mediated by protein kinase A. These studies revealed that cellular transcription factors play a significant role in regulation of FIV gene expression.
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PMID:Regulation of gene expression directed by the long terminal repeat of the feline immunodeficiency virus. 131 May 54

For immune surveillance and function to be effective, T lymphocytes constantly recirculate via lymph and blood between lymphoid organs and body tissues. To enable efficient cell movement and migration, cell adhesion to components of the basement membrane and the extracellular matrix (ECM) must be a rapid and transitory process. Whether phosphorylation and dephosphorylation of cellular proteins are involved in this phenomena was explored by monitoring the adhesion of T cells to immobilized ECM proteins. A short exposure of 51Cr-labeled human CD4+ T cells to phorbol esters in vitro induced a rapid beta 1-integrin-mediated adhesion to both fibronectin and laminin, as determined by inhibition with anti-integrin antibodies. Adhesion was reversible; detachment from the immobilized ECM ligands occurred between 20 and 120 min without further intervention. This T cell adhesion was regulated by the activation of protein kinase C because (a) staurosporine and H-7 inhibitors of protein kinase C suppressed T cell adhesion, and (b) PMA-induced down-regulation of intracellular levels of protein kinase C was associated with the abrogation of the T cell adhesiveness to fibronectin and laminin. Furthermore, inhibition of protein phosphatases activity by okadaic acid delayed the detachment of the T cells from fibronectin or laminin. Thus, we suggest that T cell-ECM interactions such as adhesion and detachment are regulated, respectively, by protein kinase C and protein phosphatases.
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PMID:Involvement of a protein kinase C and protein phosphatases in adhesion of CD4+ T cells to and detachment from extracellular matrix proteins. 132 39

Directed migration of lymphocytes from blood into lymph nodes and gut-associated lymphatic tissue, also referred to as homing, is subject to change following activation. Lymphocyte migration into lymphoid organs in vivo and binding to high endothelial venules in vitro is largely suppressed after short-term stimulation with phorbol esters. The observed functional alterations were correlated with changes in the expression of three putative homing receptors, LECAM-1 (MEL-14 antigen), LPAM-1/2 (alpha 4-integrin) and the murine CD44 (Pgp-1, H-CAM, Hermes-antigen equivalent) upon different modes of cellular activation. Expression of LECAM-1 (gp90 MEL-14), a lymphocyte adhesion molecule implicated in targeting extravasation into lymph nodes, was found to be lost almost completely within minutes after protein kinase C activation. LECAM-1 re-expression occurred within less than 24 h. Rapid loss of LECAM-1 was also observed after calcium ionophores whereas anti-CD3 or concanavalin A elicited a gradual and heterogeneous loss of LECAM-1 becoming detectable after several hours only. A number of cytokines tested were not able to induce alterations in LECAM-1 expression. In contrast, expression of LPAM-1/2 (alpha 4-integrin) and CD44 (Pgp-1, H-CAM), two adhesion molecules supposed to direct extravasation into Peyer's patches, remained stable for hours after every stimulus tested; CD44 expression gradually increased 24 h after mitogenic activation, whereas a small reduction only was observed for the expression of the alpha 4-chain under certain conditions. Thus, reduced extravasation of lymphocytes into Peyer's patches after activation is not due to a decline in the surface density of LPAM-1/2 alpha-chain or CD44 whereas alterations in migration into lymph nodes parallel the expression of LECAM-1.
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PMID:Lymphocyte activation and regulation of three adhesion molecules with supposed function in homing: LECAM-1 (MEL-14 antigen), LPAM-1/2 (alpha 4-integrin) and CD44 (Pgp-1). 137 Aug 69

The specificity and properties of a novel IgA receptor expressed on the surface of a tissue culture-adapted B cell lymphoma, T560, that originated in murine gut-associated lymphoid tissue, have been explored. Like the IgA receptors of murine T and splenic B cells studied by others, the T560 IgA receptor is trypsin sensitive and neuraminidase resistant and is up-regulated on T560 cells by exposing them overnight to high concentrations of polymeric IgA. Unlike them, the T560 IgA receptor is inhibited by low concentrations of IgM and high concentrations of IgG2a and IgG2b, binds at pH 4.0 but not at pH 8.0, is down-regulated by activation of protein kinase C and is sensitive to phosphatidylinositol-specific phospholipase C, indicating that it is glycosyl phosphatidylinositol-linked to the cell membrane. It is not a cell-bound form of galactosyl transferase, does not appear to bind to Ig through carbohydrate residues and does not react specifically with antibody to secretory component. It may be a completely new, cross-reactive receptor, perhaps related in some way to the polymeric Ig receptor or to the receptor for IgA expressed on the apical surface of Peyer's patch M cells, which is known to cross-react with IgG. Alternatively, it may be homologous to the highly IgA-specific Fc alpha R of T cells but, perhaps because of its glycosyl phosphatidylinositol linker, may have an ability to move and interact with other Ig receptors on the cell surface such that Ig bound to them are cross-inhibitory.
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PMID:A novel IgA receptor expressed on a murine B cell lymphoma. 137 46

Op18 is a highly conserved major cytosolic phosphoprotein that has been implicated in signal transduction in a wide variety of cell types. Freshly isolated peripheral blood lymphocytes (PBL) constitutively express low levels of mostly unphosphorylated Op18. After mitogenic stimulation of PBL, Op18 synthesis is induced at a time when cells are entering S-phase. In this study, we have examined the phosphorylation of Op18 in freshly isolated PBL after activation of the T cell receptor by OKT3. Quantitative analysis of Op18 phosphorylation was undertaken by metabolic labeling with 32Pi and PhosphorImager analysis of two-dimensional gels. After 10 or 15 min of activation by OKT3, one of the three major phosphorylated forms of Op18, designated Op18c, increased approximately 10-fold, which represented a most pronounced change among a large number of phosphoproteins analyzed. In time course experiments, increased Op18 phosphorylation to yield Op18c was observed as early as 2 min. Continued OKT3-induced activation for 20 to 72 h resulted in a further increase in phosphorylated Op18 forms, which paralleled new Op18 synthesis and occurred at a time when cells were entering S-phase, as determined by [3H]-thymidine incorporation. Inhibitors of lymphoid proliferation, cyclosporin A and RPM, had no effect on early (less than 15 min) phosphorylation. Addition of calphostin C, a specific inhibitor of protein kinase C, 1 min prior to stimulation of resting T cells with OKT3 completely inhibited further phosphorylation of Op18. Incubation of PBL with calphostin C for 75 min decreased constitutive levels of phosphorylated Op18. In contrast, inhibition of cyclic nucleotide-dependent protein kinases with HA1004 had no effect on Op18 phosphorylation. Activation of cAMP-dependent protein kinase with Forskolin or 8Br-cAMP did not increase Op18 phosphorylation. Our results suggest that Op18 phosphorylation is mediated by protein kinase C activation as an early event in T cell activation through the T cell receptor.
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PMID:Activation of resting peripheral blood lymphocytes through the T cell receptor induces rapid phosphorylation of Op18. 150 Jul 12

Flow cytometry and the fluorescent dyes DCF and R123 were used to examine oxygen metabolite production in human leukocytes and T-lymphoblastoid Jurkat cells, activated by PMA or by FMLP. When unseparated leukocytes were activated by PMA, oxidative products were generated not only in PMN and monocytes but also to a lower extent in lymphocytes. These responses were correlated with protein kinase C activation. PMA did not, however, induce the synthesis of reactive oxygen species in isolated lymphocytes. FMLP did not affect lymphocyte oxidative metabolism when added to the whole leukocyte mixture, but activated only the phagocyte populations. Similarly, Jurkat cells which alone were unresponsive to PMA, became strongly fluorescent when they were mixed with PMN and treated with this activator. In all cases, they did not respond to FMLP. Superoxide dismutase and catalase addition did not prevent the lymphoid cell response in the presence of phagocytes, whereas Desferal did. These data indicate that under physiological conditions, activated lymphocytes are capable of oxidative metabolism and also evidence some close relation between the leukocyte populations. We discuss the putative mechanism of oxygen metabolite generation in lymphocytes and the role of these metabolites in the immune response.
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PMID:Increased oxidative metabolism in PMA-activated lymphocytes: a flow cytometric study. 151 80

MRL-lpr/lpr (lpr) mice develop a polyclonal accumulation of abnormal peripheral T lymphocytes, which bear surface alpha beta TCR, CD3, and the B220 isoform of CD45, but lack CD4, CD8, and CD2. These T cells have a constitutively phosphorylated CD3 zeta chain and manifest a defect in signal transduction that results in a lack of IL-2 production and proliferation. We investigated whether this signaling abnormality might contribute to their accumulation via a defect in T cell elimination in the periphery. T cell deletion occurs through a process of programmed cell death with DNA degradation, or apoptosis. Viable lymphocytes from lpr mice were found to undergo rapid programmed cell death in culture within 4 h without additional activation, which was not observed in lymphocytes from normal MRL-+/+ or C57BL/6-+/+ mice. Both nonmature B220+ and mature B220- T lymphocytes from lpr mice display this accelerated programmed cell death, indicating that this is a defect affecting all peripheral T lymphocytes in lpr mice. In vitro apoptosis of lpr T cells could be inhibited with PMA, a stimulator of protein kinase C. Thus, the massive accumulation of T lymphocytes in the lymphoid tissue of lpr mice is not due to a defect in their ability to undergo programmed cell death in vitro. The activation state of lpr T cells may contribute to their rapid degradation of DNA in vitro.
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PMID:Accelerated programmed cell death of MRL-lpr/lpr T lymphocytes. 152 90

ETR103 cDNA was cloned as an immediate early gene in the course of macrophagic differentiation of HL-60 cells stimulated by TPA (12-O-tetradecanoylphorbol-13-acetate). The induction by TPA was immediate-early (within 30 min) and transient. This gene was not induced by vitamin D3 or by retinoic acid, which stimulates differentiation of HL-60 cells to the monocytic or granulocytic lineage, respectively. The ETR103 mRNA was induced by TPA in lymphoid or myeloid leukemia cell lines of several maturation stages. The induction by TPA seems to proceed by a protein kinase C-mediated mechanism, on the basis of the results obtained by using protein kinase C inhibitor (H-7), protein kinase C activator (diC8), and an activator of protein kinase A (dibutyryl cAMP). Okadaic acid, an inhibitor of protein phosphatases, also induced the ETR103 mRNA expression. The nucleotide sequence of the ETR103 cDNA reveals that ETR103 encodes a human zinc finger-containing transcription factor identical to Egr-1 and 225, which is homologous to mouse Egr-1, Zif/268, Krox-24, and TIS8, or to rat NGFI-A.
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PMID:A gene coding for a zinc finger protein is induced during 12-O-tetradecanoylphorbol-13-acetate-stimulated HL-60 cell differentiation. 156 51

We have established an RNase protection method to quantify the expression of mRNA for the human protein kinase C (PK-C) isoforms alpha, beta 1, beta 2, and gamma. This was used to investigate whether each isoform is differentially expressed during the differentiation of hematopoietic cells. Myeloid and lymphoid cells express PK-C alpha, beta 1, and beta 2 mRNAs in various proportions. PK-C gamma mRNA was detected in human brain, but not in hematopoietic cells. PK-C alpha mRNA decreases as HL-60 cells mature to a neutrophil phenotype in response to retinoic acid, but its abundance does not change during monocytic differentiation in response to vitamin D3. PK-C alpha mRNA and protein were undetectable in peripheral blood neutrophils, but are present in monocytes. The mRNAs for PK-C beta 1 and beta 2 isoforms increase during HL-60 differentiation and are expressed in both neutrophils and monocytes. Therefore, the PK-C alpha isoform is specifically down-regulated during human neutrophil terminal differentiation. These data suggest that mature neutrophil functions do not require the PK-C alpha isoform.
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PMID:Down-regulation of human protein kinase C alpha is associated with terminal neutrophil differentiation. 161 Oct 98

Although the translocation of protein kinase C and phospholipase A2 are well documented, no information is available about the possible down-modulation of transmembrane phospholipase C. We found that TPA induced a dose-dependent (10-200 nM) and time-dependent (15 min-6 h) down-modulation of transmembrane phosphoinositidase C (PLC-PI) on lymphoid cells (CEM-CM3 and WIL2-NS) and epitheloid carcinoma cells (HeLa S3) but not on human fibroblasts (MRC-5). Cell-surface expression of PLC-PI on intact cells was assayed by flow cytometry using saturating concentrations of polyclonal anti-PLC-PI antibodies and phycoerythrin-conjugate. A control phorbol-ester which does not activate protein kinase C (PKC) had no internalization effect on PLC-PI. PKC inhibitors staurosporine (2.5 nM) and H-7 (10 microM) partially inhibited the TPA effect. Cytochalasin B (40 micrograms/ml) did not modify the TPA-induced PLC-PI down-modulation. The effect of TPA on PLC-PI seems quite specific since no internalization was induced by TPA on transmembrane phosphatidylcholine-preferring PLC expression. These results show that TPA can translocate the membrane-bound PLC-PI, probably by PKC activation.
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PMID:Topological regulation of cell-membrane phosphoinositidase C. 165 Jan 98


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