Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examines how interleukin-6 (IL-6) expression by human luteinizing granulosa cells is regulated. IL-6 was assayed in culture supernatants, mRNA in cells by in situ hybridization and by a competitive reverse-transcriptase polymerase chain reaction (RT-PCR). TNF alpha (100 pg-1 ng/ml) induced IL-6 mRNA and protein. Phorbol 12-myristate 13-acetate (PMA) (50 nM) mimicked this effect. DibutyrylcAMP (1 mM) and 10 microM forskolin. C2-, C6- and C8-ceramide (15 microM), all had no effect. The inhibitor of protein tyrosine kinase (PTK), genistein (100 micrograms/ml) reduced tumor necrosis factor (TNF) effects. The inhibitors of protein kinase C (PKC) (staurosporine, 10 nM), of phospholipase C (U73122, 2 microM), of phospholipase A2 (PLA2), (indomethacin 30 microM, mepacrin 50 microM, nordihydroguaiaretic acid 10 microM, ONO-RS-082 3,5 microM), none prevented it. Hence, IL-6 is induced by TNF alpha via activation of PTK. Protein kinase A, phosphoinositide and conventional PKC, sphingomyelin and PLA2 pathways are not implicated.
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PMID:Tumor necrosis factor-alpha induces interleukin-6 mRNA and protein in human granulosa luteinizing cells via protein tyrosine kinase without involving ceramide. 908 55

Effects of uromodulin (URO) and Tamm-Horsfall protein (THP), the most abundant proteins in the urine of pregnant and normal women, respectively, on the induction of TNF-alpha secretion and tissue factor (TF) expression of human monocytes were studied. THP, URO, and its fragments stimulated human mononuclear cells to proliferate and secrete TNF-alpha. The release of URO and THP-induced TNF-alpha in monocytes was dependent upon protein tyrosine kinase activation that results in tyrosine phosphorylation. URO and THP also induced TF expression of human monocytes and monocytic cell line U937 in a dose-dependent manner. TF expression was transient, reached its peak at 6 h and declined toward basal levels by 24 h. Reverse transcriptase-PCR and dot-blot analysis confirmed the induction of TF mRNA synthesis. URO and THP-induced TF expression were inhibited by actinomycin D and pentoxifylline further supporting the requirement of de novo TF mRNA synthesis. The possibility of LPS contamination of URO and THP was excluded because: 1) URO and THP-induced TF expression were inhibited by specific Ab; 2) URO was less capable of inducing TF in HUVEC as compared with LPS; 3) polymyxin B blocked the induction of Limulus clotting by LPS but not by URO and THP; 4) both LPS-sensitive (C3H/HeN) and -resistant (C3H/HeJ) mice produced little or no TNF-alpha after URO challenge. Therefore, our findings suggest that URO and THP play a significant role in the innate immunity of the urinary system and that the immunostimulatory activity of URO is potentially useful for immunotherapy.
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PMID:Uromodulin and Tamm-Horsfall protein induce human monocytes to secrete TNF and express tissue factor. 912 Mar 6

We examined interleukin-beta (IL-1 beta) mRNA expression and protein tyrosine kinase activities induced by surface protein components of Porphyromonas gingivalis to gain insights into signaling pathways leading to macrophage responses. Reverse transcriptase-polymerase chain reaction analyses showed that native fimbriae, full-length recombinant fimbrillin, and a lectin-like 12-kDa antigen of P. gingivalis induced rapid expression of mRNA encoding IL-1 beta in BALB/c and lympopolysaccharide-hyporesponsive C3H/HeJ peritoneal macrophages. The antigens also specifically activated tyrosine kinase(s) in macrophages. The ability of the surface protein components to induce the cytokine mRNA accumulation was markedly abrogated by tyrosine kinase inhibitors. The findings reported here suggest that IL-1 beta expression in macrophages is a functional consequence of tyrosine kinase activation by the P. gingivalis surface protein components.
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PMID:Interleukin-1 gene expression in macrophages induced by surface protein components of Porphyromonas gingivalis: role of tyrosine kinases in signal transduction. 946 98

Progression of breast cancer implicates the degradation of extracellular matrix (ECM) by metallo-proteinases (MMPs), a process with important consequences on the growth and invasiveness of cancer cells in adjacent and distant sites. The isoflavone, genistein--a natural inhibitor of protein tyrosine kinase pathway--inhibits the growth of a wide range of cancer cells in vitro. The aim of this study was to investigate: i) the expression of mRNAs encoded for MMPs and their endogenous inhibitors (TIMPs) associated with pathogenesis and metastatic potential of breast cancer cells; and ii) the effect of genistein on the transcription of MMPs and TIMPs and the invasive potential of breast cancer cells. Gene expression at transcriptional level was examined in cell cultures of two epithelial breast cancer cell lines, the high invasive (ER-negative) MDA-MB-231 and the low invasive (ER-positive) MCF-7, as well as the normal mammary cells (MCF-12A) following RNA isolation and reversed transcriptase polymerase chain reaction (RT-PCR). The inhibitory effect of genistein on functional invasiveness was examined by a cell invasion assay. Cell cycle distribution showed that genistein arrested breast cancer MDA-MB-231, MCF-7 and BT-20 cells in the G2/M phase. Both normal and breast cancer cell lines express the genes of MMP-2, -9, MT1-, MT2-, MT3-MMP and TIMP-1, -2 and -3. MCF-7 express notably less MMPs than MDA-MB-231 cell line. The addition of genistein resulted in down-regulation of the transcription of all MMP genes in MDA-MB-231 and most of MMPs in MCF-7 cells. The inhibitory effect of genistein on MMPs was functionally confirmed, since it significantly reduced the invasion properties of cancer cells in vitro. The obtained results indicate that genistein may be of great value in prevention of breast cancer cell metastasis, since it represents both a transcriptional modulator of genes involved in this pathogenetic process and a suppressor of breast cancer cell invasiveness.
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PMID:Genistein suppresses the invasive potential of human breast cancer cells through transcriptional regulation of metalloproteinases and their tissue inhibitors. 1575 8

To investigate the expression profile of protein tyrosine kinases (PTKs) in normal human epidermal keratinocytes (NHEK) in response to UVA and UVB we employed a reversed transcriptase polymerase chain reaction (PCR) approach using degenerate primers derived from the conserved catalytic domain of PTKs. Quantitative real-time PCR with specific primers was used to confirm the influence of UV on the expression of the identified PTKs. Arg (Abelson-related gene, Abl2) was the PTK with the highest prevalence (30% of all PTKs) and UVA led to a further induction of Arg expression reaching nine-fold mRNA baseline expression at 17 h after irradiation. UVB was followed by an initial downregulation and a subsequent increase in Arg mRNA reaching five-fold baseline levels after 24 h. We conclude that UVA and UVB differentially modify the expression of PTKs in NHEK, and that Arg appears to have a major role in the response of keratinocytes to UV. These results provide a basis for further studies of PTK in UV-induced signaling that regulates protective responses, cell growth and carcinogenesis in the skin.
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PMID:Ultraviolet-A and -B differentially modify the tyrosine-kinase profile of human keratinocytes and induce the expression of Arg+. 1841 39