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)

The human G0/G1 switch (G0S) gene, G0S24, and its rodent immediate-early homolog (TIS11, TTP, NUP475) are part of a mammalian gene family whose members encode CCCH zinc finger domains and domains similar to part of the large subunit of RNA polymerase II and to the Mei2 regulator of G1 arrest in fission yeast. We compared the RNA expression of G0S24 with that of other G0S genes in cultured blood mononuclear cells and examined the levels of various RNA processing intermediates. Freshly isolated cells contained high levels of several G0S RNAs, which declined by 24 h, suggesting transient spontaneous stimulation during cell purification (Heximer et al., 1996). However, in cells preincubated for 24 h, G0S24 RNA levels remained much higher than those of other G0S genes (107+/-42 x 10(6) molecules/microg of RNA); stimulation with lectin (Con-A) further increased G0S24 RNA, much of which remained nuclear. Like those of FOS/G0S7, EGR1/G0S30 and of the gene encoding the regulator of G protein signalling 1 (RGS1), G0S24 RNA levels increased more in response to a protein kinase C activator than to a calcium ionophore, whereas the opposite held for FOSB/G0S3 and RGS2/G0S8. With appropriate PCR primer pairs, we showed a G0S24 RNA processing intermediate, which crossed the exon-1/intron boundary, and nonpolyadenylated nuclear RNA extending into the 3' flank, where there is a second CpG island. The concentration of the latter intermediate (1.2+/-0.2 x 10(6) molecules/microg of RNA), which increased transiently on cell stimulation, did not account for all G0S24 nuclear RNA. The levels of G0S24 RNA and both intermediates were increased by the protein synthesis inhibitor cycloheximide, consistent with regulation by a labile repressor.
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PMID:Expression and processing of G0/G1 switch gene 24 (G0S24/TIS11/TTP/NUP475) RNA in cultured human blood mononuclear cells. 953 5

Recent research on alpha-tocopherol has revealed specific cellular functions of this compound belonging to the vitamin E family. Alpha-tocopherol can act as a radical scavenger, as a pro-oxidant, as an anti-alkylation agent and, most important, by mechanisms that are independent of the above properties. To the last group belong protein kinase C and 5-lipoxygenase inhibition at post-translational level, as well as alpha-tocopherol activation of protein phosphatase 2A and diacylglycerol kinase. Furthermore, at transcriptional level, several genes (CD36, alpha-TTP, alpha-tropomyosin, and collagenase) are modulated by alpha-tocopherol. These effects result in inhibition of smooth muscle cell proliferation, platelet aggregation, and monocyte adhesion and may be related to the alleged protection of atherosclerosis by vitamin E. On the other side, epidemiological and intervention studies have shown some inconsistent results. Rather than disregarding vitamin E as a means to protect against atherosclerosis progression, it would be wiser to better design clinical trials based on current knowledge of the biological properties of the molecule.
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PMID:Vitamin E 80th anniversary: a double life, not only fighting radicals. 1179 98

Molecules provided with an antioxidant function may have additional properties, the latter being sometimes of greater importance than the former. In the last ten years, alpha-tocopherol has revealed precise cellular functions, some of which are independent of its antioxidant/radical scavenging ability. At the posttranslational level, alpha-tocopherol inhibits protein kinase C and 5-lipoxygenase and activates protein phosphatase 2A and diacylglycerol kinase. Some genes (CD36, alpha-TTP, alpha-tropomyosin, and collagenase) are affected by alpha-tocopherol at the transcriptional level. alpha-Tocopherol also induces inhibition of cell proliferation, platelet aggregation and monocyte adhesion. These effects are unrelated to the antioxidant activity of vitamin E, but rather are believed to be a result of specific interactions of vitamin E with components of the cell, e. g. proteins, enzymes and membranes. This review focuses on novel non-antioxidant functions of alpha-tocopherol and discusses the possibility that many of the effects previously attributed to the antioxidant functions can also be explained by non-antioxidant mechanisms.
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PMID:The 80th anniversary of vitamin E: beyond its antioxidant properties. 1203 35

Molecules in biological systems often can perform more than one function. In particular, many molecules have the ability to chemically scavenge free radicals and thus act in the test tube as antioxidant, but their main biological function is by acting as hormones, ligands for transcription factors, modulators of enzymatic activities or as structural components. In fact, oxidation of these molecules may impair their biological function, and cellular defense systems exist which protect these molecules from oxidation. Vitamin E is present in plants in 8 different forms with more or less equal antioxidant potential (alpha-, beta-, gamma-, delta-tocopherol/tocotrienols); nevertheless, in higher organisms only alpha-tocopherol is preferentially retained suggesting a specific mechanism for the uptake for this analogue. In the last 20 years, the route of tocopherol from the diet into the body has been clarified and the proteins involved in the uptake and selective retention of alpha-tocopherol discovered. Precise cellular functions of alpha-tocopherol that are independent of its antioxidant/radical scavenging ability have been characterized in recent years. At the posttranslational level, alpha-tocopherol inhibits protein kinase C, 5-lipoxygenase and phospholipase A2 and activates protein phosphatase 2A and diacylglycerol kinase. Some genes (e. g. scavenger receptors, alpha-TTP, alpha-tropomyosin, matrix metalloproteinase-19 and collagenase) are modulated by alpha-tocopherol at the transcriptional level. alpha-Tocopherol also inhibits cell proliferation, platelet aggregation and monocyte adhesion. These effects are unrelated to the antioxidant activity of vitamin E, and possibly reflect specific interactions of alpha-tocopherol with enzymes, structural proteins, lipids and transcription factors. Recently, several novel tocopherol binding proteins have been cloned, that may mediate the non-antioxidant signaling and cellular functions of vitamin E and its correct intracellular distribution. In the present review, it is suggested that the non-antioxidant activities of tocopherols represent the main biological reason for the selective retention of alpha-tocopherol in the body, or vice versa, for the metabolic conversion and consequent elimination of the other tocopherols.
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PMID:Non-antioxidant activities of vitamin E. 1513 10

Several genes are regulated by tocopherols which can be categorized, based on their function, into five groups: genes that are involved in the uptake and degradation of tocopherols (Group 1) include alpha-tocopherol transfer protein (alpha-TTP) and cytochrome P450 (CYP3A); genes that are associated with lipid uptake and atherosclerosis (Group 2) include CD36, SR-BI and SR-AI/II. Genes that modulate the expression of extracellular proteins (Group 3) include tropomyosin, collagen(alpha1), MMP-1, MMP-19 and connective tissue growth factor (CTGF). Genes that are related to inflammation, cell adhesion and platelet aggregation (Group 4) include E-selectin, ICAM-1, integrins, glycoprotein IIb, II-2, IL-4 and IL-beta. Group 5 comprises genes coding for proteins involved in cell signaling and cell cycle regulation and consists of PPAR-gamma, cyclin D1, cyclin E, Bcl2-L1, p27 and CD95 (Apo-1/Fas ligand). The expression of P27, Bcl2, alpha-TTP, CYP3A, tropomyosin, II-2, PPAR-gamma, and CTGF appears to be up-regulated by one or more tocopherols whereas all other listed genes are down-regulated. Several mechanisms may underlie tocopherol-dependent gene regulation. In some cases protein kinase C has been implicated due to its deactivation by alpha-tocopherol and its participation in the regulation of a number of transcription factors (NF-kappaB, AP-1). In other cases a direct involvement of PXR/RXR has been documented. The antioxidant responsive element (ARE) appears in some cases to be involved as well as the transforming growth factor beta responsive element (TGF-beta-RE). This heterogeneity of mediators of tocopherol action suggests the need of a common element that could be a receptor or a co-receptor, able to interact with tocopherol and with transcription factors directed toward specific regions of promoter sequences of sensitive genes. Here we review recent results of the search for molecular mechanisms underpinning the central signaling mechanism.
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PMID:Regulation of gene expression by alpha-tocopherol. 1531 6

Tristetraprolin/zinc finger protein 36 (TTP/ ZFP36) binds and destabilizes some proinflammatory cytokine mRNAs. TTP-deficient mice develop a profound inflammatory syndrome due to excessive production of proinflammatory cytokines. TTP gene expression is induced by various factors including insulin, cinnamon, and green tea extracts. Previous studies have shown that TTP is highly phosphorylated in vivo and multiple phosphorylation sites are identified in human TTP. This study evaluated the potential protein kinases that could phosphorylate recombinant TTP in vitro. Motif scanning suggested that TTP was a potential substrate for various kinases. SDS-PAGE showed that in vitro phosphorylation of TTP with p42 and p38 MAP kinases resulted in visible electrophoretic mobility shift of TTP to higher molecular masses. Autoradiography showed that TTP was phosphorylated in vitro by GSK3b, PKA, PKB, PKC, but not Cdc2, in addition to p42, p38, and JNK. These results demonstrate that TTP is a substrate for a number of protein kinases in vitro.
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PMID:Phosphorylation of recombinant tristetraprolin in vitro. 1807 86