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)

Human interferon-gamma (IFN-gamma) is an important immunomodulatory protein produced predominantly by T cells and large granular lymphocytes (LGLs). Whereas large amounts of data have been accumulated regarding IFN gamma gene expression in these two cell types, little information about IFN gamma expression in other cell types exists. In this study, we have analyzed the production of IFN gamma by the Epstein-Barr virus (EBV)-positive B-cell line, JLP(c), derived from a patient with Burkitt's lymphoma, and another human B-cell line, PA682BM-1, which was derived from an acquired immunodeficiency syndrome patient. Southern blot analysis indicates the presence of an Ig heavy chain gene rearrangement, but no rearrangement of the T-cell receptor beta chain gene or IFN gamma gene in these B-cell lines. Both cell lines were found to express surface IgD and other B-cell surface markers, thus confirming their B-cell lineage. Analysis for surface Ig, cytoplasmic Ig, and secreted Ig indicates that the two cell lines are in relatively early stages of the B-cell differentiation pathway. We now report that PA682BM-1 can be triggered by the protein kinase C (PKC) activators, phorbol 12-myristate 13-acetate (PMA) and (-)Indolactam-v, to secrete IFN gamma, whereas JLP(c) cells spontaneously produce low levels of IFN gamma that can be enhanced by PKC activators and interleukin-2 (IL-2). After activation of the cell lines with IL-2, (-)Indolactam-v, and PMA, increases in cytoplasmic messenger RNAs (mRNAs) of IFN gamma and the IL-2 receptor chains were also observed. The induction of IFN gamma mRNA and protein by IL-2 was completely blocked by a monoclonal antibody to IL-2 receptor p75 (beta chain), but not by the monoclonal antibody to p55 (alpha chain). Analysis of IFN gamma genomic DNA indicates that the gene is not amplified, but that hypomethylation in the 5' noncoding region of the IFN gamma gene has occurred in the B-cell line from the Burkitt's lymphoma patient that spontaneously produces IFN gamma. This finding suggests that the methylation state of the promoter region may play an important role in the control of IFN gamma gene expression in B cells.
 ...
PMID:Interferon-gamma gene expression in human B-cell lines: induction by interleukin-2, protein kinase C activators, and possible effect of hypomethylation on gene regulation. 132 3

This study examines the hypothesis that interferon-gamma (IFN-gamma) induces protein phosphorylation as part of the signal transduction pathway used to activate U937 cells. U937 cells labeled with 32Pi were treated with IFN-gamma, proteins were separated by two-dimensional polyacrylamide gel electrophoresis, and the pattern of protein phosphorylation was determined by autoradiography and computer-assisted two-dimensional densitometry. IFN-gamma (100 U/ml) induced phosphorylation of multiple proteins between 15 and 60 min, and the proteins were all dephosphorylated by 120 min. The pattern of proteins phosphorylated in the presence of ionomycin or PMA differed from that of IFN-gamma. Inhibition of protein kinase C activity by 1-(5-isoquinolinesulfonyl)2-methyl piperazine (H-7), inhibition of calcium-calmodulin-dependent protein kinase by N-(6-aminohexyl)-5-chloro-naphthalenesulfonamide (W-7), and inhibition of calcium redistribution by 8-(diethylamino)-octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) did not inhibit the majority of IFN-gamma-induced protein phosphorylation. These data indicate that IFN-gamma induces protein phosphorylation in U937 cells by activation of a kinase different from, or in addition to, protein kinase C or calcium-calmodulin-dependent kinase.
 ...
PMID:Interferon-gamma induces phosphorylation of multiple small-molecular-weight proteins in U937 cells. 133 Dec 58

Human interferon-alpha A/D (Bg/II) (IFN-alpha A/D) and mouse interferon-gamma (IFN-gamma) are shown to induce xanthine dehydrogenase (XD) mRNA in L929 fibroblastic cells. XD mRNA accumulation after IFN-alpha A/D treatment is relatively fast, being already evident after 4 h and reaching its maximum after 24 h. IFN-alpha A/D is active in inducing XD mRNA at 0.1 unit/ml and it is maximally active at 10(3) units/ml. The half-life of the XD message is unaffected by IFN-alpha A/D treatment, whereas the transcriptional activity of the XD gene and the concentrations of XD heterogeneous nuclear RNA are increased by 2- and 6-fold respectively. The effect of IFN-alpha A/D on XD mRNA is insensitive to cycloheximide, suggesting that protein synthesis de novo is not required. Experiments conducted with specific inhibitors suggest that protein kinase C, cyclic AMP and arachidonic acid metabolites derived from lipoxygenase or cyclooxygenase do not act as second-messenger molecules in the induction of XD mRNA by IFN-alpha A/D. XD mRNA is also induced in NIH3T3 fibroblastic cells, but not in F9 teratocarcinoma or B16 melanoma cells after treatment with IFN-alpha A/D. NIH3T3 are the only cells so far tested that have detectable XD and xanthine oxidase activities under basal conditions and after IFN-alpha A/D treatment, although their responsiveness to the cytokine is much less than that observed in L929 cells.
 ...
PMID:Interferons induce xanthine dehydrogenase gene expression in L929 cells. 137 96

Continuous proliferation of the immortalized myeloid progenitor cell line FDC-P1 depends on stimulation with either interleukin-3 (IL-3) or granulocyte-macrophage colony stimulating factor (GM-CSF). Two other cytokines, interferon-gamma (IFN-gamma) and IL-4, were found to prolong FDC-P1 survival for several days. Surviving cells incorporated [3H]thymidine and a minority completed up to 3 cell divisions before dying. This transient proliferative response was a direct effect of IFN-gamma and IL-4 since these cytokines did not induce production of detectable IL-3 or GM-CSF and the response was unaffected by cell concentration. IL-6, a constitutive product of FDC-P1 cells whose secretion was increased by IL-3, GM-CSF and IL-4 but not by IFN-gamma, was not responsible for the proliferative response. FDC-P1 lines that constitutively expressed the cell cycle-associated oncogene myc or the survival-associated oncogene bcl-2 also responded only transiently to IFN-gamma or IL-4, indicating that expression of these genes did not complement the signals delivered by IFN-gamma or IL-4. By contrast, the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) prolonged survival of FDC-P1 cells on its own and potentiated the response to IFN-gamma or IL-4, although the combination of stimuli did not support long-term growth. It is concluded that IFN-gamma and IL-4 trigger only some of the signalling events that lead to mitogenesis; these events are complemented by stimulation with PMA but additional signals are required for sustained proliferation.
 ...
PMID:Survival of the myeloid progenitor cell line FDC-P1 is prolonged by interferon-gamma or interleukin-4. 138 29

Anti-lymphocyte and anti-thymocyte globulins (ATG) are currently used as immunosuppressive agents in organ transplantation. Their administration in vivo may induce not only lymphocyte depletion but also functional effects which were investigated in the present study. In vitro ATG inhibited T-cell proliferation induced by monocyte-dependent T-cell mitogens, like CD3 antibodies, phytohaemagglutinin (PHA) and concanavalin A (Con A), by monocyte-independent mitogens, like CD2 antibodies, or by protein kinase C activators (phorbol esters) associated with a calcium ionophore. The inhibitory effect of ATG was therefore not solely accounted for by a suppression of co-stimulatory signals delivered by monocytes, but rather implied a direct action on T cells. Addition of recombinant human interleukin-2 (rIL-2) did not overcome the inhibition. Suppression of T-cell proliferation by ATG was characterized by normal RNA synthesis and IL-2 secretion contrasting with markedly reduced expression of the CD25 protein [p55, the alpha-chain of interleukin-2 receptor (IL-2R)] both in cytoplasm and on T-cell membrane, as well as a decreased secretion of interferon-gamma (IFN-gamma). Northern blot analysis revealed increased levels of CD25 and IFN-gamma mRNA, suggesting a post-transcriptional inhibition of these molecules, whereas IL-2 mRNA levels were unchanged. These data demonstrate that inhibition of T-cell proliferation by ATG can be attributed primarily to a post-transcriptional defect of CD25 expression, implying a novel mechanism different from those described with other immunosuppressive agents. Blocking of T-cell proliferation in the late G1 phase of the cell cycle may contribute to the immunosuppressive activity of ATG in prophylactic treatment of allograft rejection.
 ...
PMID:Inhibition of CD25 (IL-2R alpha) expression and T-cell proliferation by polyclonal anti-thymocyte globulins. 139 65

Interleukin-1 (IL-1) is believed to be involved in articular destruction in rheumatoid arthritis. HLA-class II antigens are expressed on synovial cells of patients with RA. The relation between the production of IL-1 and expression of HLA-class II antigens was studied. Synovial cells of rheumatoid patients appeared to express HLA-DR and DQ antigens to a significantly greater extent than those of osteoarthritic patients. These cells produced IL-1 following interferon-gamma (IFN-gamma) stimulation and there was synergistic enhancement of production induced by IFN-gamma and monoclonal antibodies to HLA-DR or DQ antigens in combination. In the intracellular signal transduction mechanism for the production of IL-1 beta by these cells following IFN-gamma stimulation, protein kinase C and calmodulin may be involved as second messengers.
 ...
PMID:[Induction of interleukin-1 production in the cultured synovial cells from patients with rheumatoid arthritis]. 141 92

The role of protein kinase C (PKC) in the induction of nitric oxide synthesis by interferon-gamma (IFN-gamma) was investigated using two murine macrophage cell lines, J774 and RAW 264.7. Nitric oxide (NO) production was markedly reduced by a PKC inhibitor, Ro31-8220 in a dose-dependent manner. Incubation of cells with IFN-gamma resulted in translocation of PKC to the cell membrane. Prolonged incubation of cells with a high concentration of phorbol ester, which down-regulated PKC activity, also reduced nitric oxide production. These findings provide evidence that PKC is involved in the induction of nitric oxide synthesis by IFN-gamma.
 ...
PMID:The role of protein kinase C in the induction of nitric oxide synthesis by murine macrophages. 144 68

Multinucleated giant cells (MGCs) are an integral part of the host immune response to infectious disease and are seen in granulomas induced by pathogens and inorganic substances. We have developed a novel system for the production and study of MGCs: Peripheral blood monocytes, when cultured in the presence of anti-class II major histocompatibility complex monoclonal antibodies (MHC mAb's) and lymphocyte-conditioned medium form MGCs within 48 h. MGC formation was strictly dependent on the presence of anti-class II MHC mAb's and lymphocyte-conditioned medium. MGC formation was not induced by mAb's to other monocyte surface proteins. None of the previously identified macrophage fusion factors (calcitriol, interleukin 4, interferon-gamma) were able to substitute for the lymphocyte-conditioned medium in our assay; however, the conditioned medium could be replaced by the phorbol ester phorbol 12-myristate 13-acetate. We have also demonstrated that the induction of MGCs by anti-class II MHC antibody and phorbol ester requires protein kinase C activity, because MGC formation was totally inhibited by the protein kinase C inhibitors staurosporine and H-7. In analyzing the signal induced by anti-class II MHC mAb's we have demonstrated that cross-linking of the class II MHC antigens with intact mAb's, or with F(ab')2 fragments of anti-class II MHC mAb's and F(ab')2 fragments of rabbit antimouse (RAM) immunoglobulin G, produced an intracellular calcium rise. Furthermore, using the calcium channel blocker verapamil, it was demonstrated that calcium channel activity is necessary for MGC formation. These data support the view that MGC formation is a tightly regulated differentiative pathway of peripheral blood monocytes that is dependent on protein kinase C second messenger systems and involves an increase in intracellular calcium concentration.
 ...
PMID:Anti-class II MHC antibody induces multinucleated giant cell formation from peripheral blood monocytes. 154 3

This study investigated the intracellular signal transduction regulating the appearance of HLA class I antigens on Huh 6 cells induced by interferon-gamma. The expression was blocked by a protein kinase C inhibitor, H-7, but not by a calmodulin antagonist, W-7, nor by a protein kinase A inhibitor, H-8, at low dose. The antigen expression was induced by a direct activator of protein kinase C, phorbol myristate acetate, but not by calcium ionophore A23187 nor an analog of cAMP, dbcAMP. Therefore, we concluded that protein kinase C is involved in the expression of HLA class I antigens on Huh 6 cells induced by interferon-gamma but Ca(2+)-calmodulin and cAMP are not.
 ...
PMID:Signal transduction pathways in the induction of HLA class I antigen expression on Huh 6 cells by interferon-gamma. 164 5

The ability of the 134-2C2 monoclonal antibody (mAb; CD26) to transmit an activation signal and to affect T cell proliferation has been studied. The 134-2C2 mAb, although not being mitogenic by itself, is able to increase the proliferation of purified T cells in the presence of exogenous interleukin 2 (IL2) or phorbol 12-myristate 13-acetate (PMA). No effect of our mAb was observed on the proliferation of T cells induced by other stimuli such as Sepharose-bound CD3 mAb, phytohemagglutinin or calcium ionophore. Since the co-stimulatory effect of 134-2C2 mAb on PMA-induced T cell proliferation was strongly inhibited by an anti-Tac antibody, its involvement on the IL2/IL2 receptor pathway was investigated. An increased IL2 secretion in T cells cultured with PMA plus 134-2C2 mAb was observed and Northern blot analysis showed that the mAb 134-2C2 acts synergistically with PMA favoring the induction of both IL2 and interferon-gamma mRNA synthesis, as well as the enhancement of IL2 receptor and transferrin receptor mRNA expression. Studies on mechanisms implicated in signal transduction showed that 134-2C2 mAb modifies neither intracellular calcium levels nor phosphoinositide breakdown. Additionally, no effect was exerted on protein kinase C translocation. These data suggest that the CD26 antigen is involved in T cell activation in an IL2/IL2 receptor-dependent pathway.
 ...
PMID:Induction of interleukin 2 (IL 2) and interferon-gamma and enhancement of IL 2 receptor expression by a CD26 monoclonal antibody. 167 34


1 2 3 4 5 6 7 8 9 10 Next >>