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

---

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

Ginsenoside-Rg1 (G-Rg1) present in the roots of Panax ginseng (C. A. Meyer) has been shown to induce the enzyme activity of tyrosine aminotransferase (TAT) EC(2.6.1.5) in rat hepatocyte cultures. Thus, we investigated whether the inductive effect of G-Rg1 may act through glucocorticoid receptor- or cAMP-mediated action mechanism in the hepatocyte cultures. G-Rg1 induced the TAT activity by 2-fold with a similar time course to that of dexamethasone in the cell cultures. This effect of G-Rg1 was abolished to the basal level when RU486, a specific glucocorticoid antagonist was added to 10(-5)M. Furthermore, the additive effect of G-Rg1 and dexamethasone was inhibited as well by RU486. G-Rg1 and dibutyryl-cAMP (Bt2-cAMP) also revealed an additive effect but this additive effect was inhibited only to the G-Rg1-induced level by Rp-cAMPS, a specific inhibitor of protein kinase A. From these results, we suggest that the action mechanism of G-Rg1 leading to the induction of TAT activity may be mediated through glucocorticoid receptor binding and may not directly act through cAMP-mediated induction mechanism.
...
PMID:Inductive effect of ginsenoside-Rg1 on tyrosine aminotransferase gene expression in rat primary hepatocyte cultures. 786 12

Transcription of the rat tyrosine aminotransferase gene (TAT) is stimulated in liver by glucocorticoid hormones or by cAMP-increased protein kinase A activity via enhancers located 2.5 kilobases (kb) and 3.6 kb upstream of the start site of transcription. The proteins mediating induction have been characterized, and protein binding in the two enhancer regions has been analyzed in vivo and in vitro. The TAT gene is therefore a useful model system with which to study cross-talk between different signal transduction pathways. We find that activation of the second messenger pathway leading from protein kinase C to the transcription factor AP-1 by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) impairs induction of the TAT gene both by glucocorticoid hormones and cAMP. The effects of TPA treatment on chromatin structure of the TAT gene and protein-DNA interactions in vivo were assayed. Under conditions in which TPA impairs glucocorticoid induction of TAT mRNA, the glucocorticoid receptor and other proteins binding within the glucocorticoid-inducible enhancer occupy their binding sites, indicating that inhibition occurs at a later step necessary for transcriptional stimulation. On the other hand, inhibition of cAMP induction correlates with reduced occupancy of the cAMP response element in vivo.
...
PMID:Cross-talk modulation of signal transduction pathways: two mechanisms are involved in the control of tyrosine aminotransferase gene expression by phorbol esters. 791 48

We have previously shown that insulin is less effective in inducing expression of several genes in H4 hepatoma cells with reduced functional protein kinase-C (PKC) activity. However, other reports suggest that insulin regulation of gene transcription is not PKC dependent. Insulin and phorbol 12-myristate 13-acetate (PMA) rapidly inhibit transcription of the tyrosine aminotransferase and albumin genes. Prolonged PMA pretreatment, to desensitize cells to PMA, resulted in a loss of insulin ability to inhibit albumin transcription. Insulin was still able to inhibit tyrosine aminotransferase transcription, but less than in non-PMA-pretreated cells, and there was also a slight decrease in the ability of insulin to inhibit phosphoenolpyruvate carboxykinase transcription. We previously demonstrated decreased responsiveness of PMA-induced gene expression in insulin-desensitized cells. In the present work, using insulin-desensitized H4 cells (insulin pretreatment for 24 h), subsequent treatment with PMA did not alter phosphoenolpyruvate carboxykinase transcription rates, whereas PMA did inhibit tyrosine aminotransferase transcription rates to an extent similar to observed in nonpretreated cells. Unexpectedly, there was a significant increase in albumin transcription after PMA addition to insulin-pretreated cells. These findings support our hypothesis that the role of PKC in the regulation of gene expression by insulin varies for different insulin-regulated genes.
...
PMID:Evidence for diverse roles of protein kinase-C in the inhibition of gene expression by insulin: the tyrosine aminotransferase, albumin, and phosphoenolpyruvate carboxykinase genes. 798 15

In somatic hybrids between fibroblast microcells and rat hepatoma cells, tissue-specific extinguisher 1 (TSE1), localized to mouse chromosome 11, extinguishes the expression of tyrosine aminotransferase and phospho(enol)pyruvate carboxykinase. Recently, it was demonstrated that TSE1 corresponds to R1 alpha, a regulatory subunit of protein kinase A. Here, we have analyzed whether R1 alpha could play a role in differentiation of the hepatocyte. It is known that the TSE1/R1 alpha target genes belong to the group of neonatal functions that are repressed until birth. High expression of R1 alpha characterizes fetal-type BW1J hepatoma cells in which the neonatal target genes are silent. This R1 alpha is active in trans to extinguish these genes in hybrids between BW1J and Fao adult-type rat hepatoma cells. Reexpression of the target genes is correlated with loss of R1 alpha and/or overexpression of the mRNA for the hepatocyte-enriched transcription factors HNF4 and HNF3 alpha. Phenylalanine hydroxylase is shown to be another function negatively regulated by R1 alpha. In BW cells in which expression of phenylalanine hydroxylase has been activated (after either 5-aza-cytidine treatment or transfection with genomic DNA from adult-type hepatoma cells), no down-regulation of R1 alpha expression occurs: an independent mechanism overcomes R1 alpha repression. Finally, dedifferentiated derivatives of the adult-type rat hepatoma cells express neither the R1 alpha target genes nor the R1 alpha gene itself. Thus, in three different situations in which modulation of R1 alpha expression could be anticipated, it fails to occur.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Constancy of expression of the protein kinase A regulatory subunit R1 alpha in hepatoma cell lines of different phenotypes. 812 92

The effect of anisoosmolarity on the abundance of various mRNA species was examined in perfused rat liver and H4IIE rat hepatoma cells. Hyperosmotic exposure (385 mosmol/l) of isolated rat livers increased mRNA levels for tyrosine aminotransferase (TAT) by 246% and those for phosphoenolpyruvate carboxykinase (PEPCK) by 186%, whereas hypoosmotic exposure (225 mosmol/l) decreased their levels to 43% and 42%, respectively. mRNA levels for fructose-1,6-bisphosphatase (FBP), argininosuccinate lyase (ASL), argininosuccinate synthetase (ASS), glutamine synthetase (GS), glutaminase (GA) and glucokinase (GK) were largely unaffected. In H4IIE cells the modulation of TAT and PEPCK mRNA levels by anisoosmotic exposure was similar to that found in perfused rat liver. ASL and glutaminase mRNA levels were influenced in an opposite manner. The effects of anisoosmolarity on PEPCK mRNA levels in H4IIE cells were largely abolished in the presence of the protein kinase inhibitors H-7, H-89 and HA-1004. Other protein kinase inhibitors such as Go-6850, KN-62, Rp-8-CPT-cAMPS, rapamycin, wortmannin, genistein or herbimycin did not prevent the osmosensitivity of PEPCK mRNA levels. Also pertussis and cholera toxin, vanadate and colchicine did not affect the osmosensitivity of PEPCK mRNA levels. The data suggest that anisoosmotic exposure acts on the levels of some but not all mRNA species and that this action may involve changes in protein phosphorylation. They further indicate that the recently identified osmosensitive signal transduction pathway which involves a G-protein and tyrosine kinase dependent activation of mitogen-activated protein kinases is apparently not involved in the osmoregulation of PEPCK mRNA levels.
...
PMID:Anisoosmotic regulation of hepatic gene expression. 892 14

We have shown that the sensitivity of isolated hepatocytes and H4 hepatoma cells to cyclic AMP is different. In terms of activation of tyrosine aminotransferase at mRNA and activity level in response to cyclic AMP, isolated hepatocytes are 10-fold more sensitive. Hepatocytes and H4 hepatoma cells show similar sensitivities to cyclic AMP at the level of protein kinase A activation and phosphorylation of cyclic AMP response element binding protein (CREB) and the differential sensitivity must reside at other sites. The consequences of these findings to studies of control phenomena at the transcriptional level is discussed.
...
PMID:Rat primary hepatocytes and H4 hepatoma cells display differential sensitivity to cyclic AMP at the level of expression of tyrosine aminotransferase. 983 81

The retinoblastoma tumor suppressor protein (pRB) negatively regulates early-G(1) cell cycle progression, in part, by sequestering E2F transcription factors and repressing E2F-responsive genes. Although pRB is phosphorylated on up to 16 cyclin-dependent kinase (Cdk) sites by multiple G(1) cyclin-Cdk complexes, the active form(s) of pRB in vivo remains unknown. pRB is present as an unphosphorylated protein in G(0) quiescent cells and becomes hypophosphorylated (approximately 2 mol of PO(4) to 1 mol of pRB) in early G(1) and hyperphosphorylated (approximately 10 mol of PO(4) to 1 mol of pRB) in late G(1) phase. Here, we report that hypophosphorylated pRB, present in early G(1), represents the biologically active form of pRB in vivo that is assembled with E2Fs and E1A but that both unphosphorylated pRB in G(0) and hyperphosphorylated pRB in late G(1) fail to become assembled with E2Fs and E1A. Furthermore, using transducible dominant-negative TAT fusion proteins that differentially target cyclin D-Cdk4 or cyclin D-Cdk6 (cyclin D-Cdk4/6) and cyclin E-Cdk2 complexes, namely, TAT-p16 and TAT-dominant-negative Cdk2, respectively, we found that, in vivo, cyclin D-Cdk4/6 complexes hypophosphorylate pRB in early G(1) and that cyclin E-Cdk2 complexes inactivate pRB by hyperphosphorylation in late G(1). Moreover, we found that cycling human tumor cells expressing deregulated cyclin D-Cdk4/6 complexes, due to deletion of the p16(INK4a) gene, contained hypophosphorylated pRB that was bound to E2Fs in early G(1) and that E2F-responsive genes, including those for dihydrofolate reductase and cyclin E, were transcriptionally repressed. Thus, we conclude that, physiologically, pRB is differentially regulated by G(1) cyclin-Cdk complexes.
...
PMID:Differential regulation of retinoblastoma tumor suppressor protein by G(1) cyclin-dependent kinase complexes in vivo. 1141 52

The structural similarity of cyclic GMP-dependent protein kinase (cGPK) and cyclic AMP-dependent protein kinase (cAPK) has made it difficult to study cGPK pathways independent of those mediated by cAPK, primarily due to the lack of potent and selective cGPK inhibitors. We recently reported a novel peptide library screen specifically designed to select for tight-binding peptides that identified selective inhibitors of cGPK [Proc Natl Acad Sci USA, 97 (2000) 14772]. Iterative deconvolution of octameric library arrays on paper identified the sequence LRK(5)H (W45). Binding of W45 to cGPK resulted in selective inhibition of the kinase, with K(i) values of 0.8 microM and 560 microM for cGPK and cAPK, respectively. Cellular internalization of highly charged W45 was accomplished by N-terminal fusion of membrane translocation sequences from either the human immunodeficiency virus tyrosine aminotransferase protein (47-59) DT-2 or from the Drosophila Antennapedia homeodomain (43-58) DT-3, respectively. For both fusion peptides, DT-2 and DT-3, we observed a potentiating effect with respect to the inhibitory potency, with K(i) values 40- to 80-fold lower than W45. Fluorescein-labeled DT-2 and DT-3 demonstrated rapid translocation through the cytosol and nuclei in a time-dependent manner using cultured cells and intact tissue samples (cerebral arteries). The physiological effects of DT-2 and DT-3 as selective cGPK inhibitors in smooth muscle were studied in small intact arteries. Nitric oxide, a cyclic GMP/cGPK activator, elicited a concentration-dependent dilation of isolated rat cerebral arteries, which was markedly inhibited by DT-2 and DT-3. Collectively, these results indicate that DT-2 and DT-3 effectively inhibit nitric oxide-induced vasodilation, further emphasizing the central role for cGPK in the modulation of vascular contractility.
...
PMID:Exploring the mechanisms of vascular smooth muscle tone with highly specific, membrane-permeable inhibitors of cyclic GMP-dependent protein kinase Ialpha. 1219 12

We report the first mutational study of thymidine kinase 1 (TK1) performed in human solid tumors. We sequenced cDNAs representing the complete coding region of TK1 in human breast (n=22) and colorectal (n=26) cancer. Codon 106 near the ATP binding site constantly differed (ATG --> GTG; Met --> Val) from the one deposited by Bradshaw and Deininger in the Genbank database (Accession number NM_003258). Silent polymorphisms at codon 11 (CCC --> CCT; Pro --> Pro) and codon 75 (GCG --> GCA; Ala --> Ala) were frequently detected in tumors as well as in normal tissues. In breast cancer the two polymorphisms were observed in 63.6% of the samples analyzed. No significant association could be found between polymorphisms and TK activity. In colorectal cancer the incidence of the two changes was 73.1% and 69.2%, respectively. Interestingly, one colon cancer with high cytosolic TK activity displayed two missense mutations located in and near the putative phosphorylation site by tyrosine kinase (s) (TAT --> CAT; Tyr --> His) and by cAMP-, cGMP-dependent protein kinase (TAC --> TGC; Tyr --> Cys), respectively; adjacent normal mucosa showed no mutation. This may open new avenues that imply TK1 activity in tumor cell proliferation.
...
PMID:Mutation analysis in the coding sequence of thymidine kinase 1 in breast and colorectal cancer. 1269 56

Apactin is an 80-kDa type I membrane glycoprotein derived from pro-Muclin, a precursor that also gives rise to the zymogen granule protein Muclin. Previous work showed that apactin is efficiently removed from the regulated secretory pathway and targeted to the actin-rich apical plasma membrane of the pancreatic acinar cell. The cytosolic tail (C-Tail) of apactin consists of 16 amino acids, has Thr casein kinase II and Ser protein kinase C phosphorylation sites, and a C-terminal PDZ-binding domain. Secretory stimulation of acinar cells causes a decrease in Thr phosphorylation and an increase in Ser phosphorylation of apactin. Fusion peptides of the C-Tail domain pulldown actin, ezrin, and EBP50/NHERF in a phosphorylation-dependent manner. HIV TAT-C-Tail fusion peptides were used as dominant negative constructs on living pancreatic cells to study effects on the actin cytoskeleton. During secretory stimulation, TAT-C-Tail-Thr/Asp phosphomimetic peptide caused an increase in actin-coated zymogen granules at the apical surface, while TAT-C-Tail-S/D phosphomimetic peptide caused a broadening of the actin cytoskeleton. These data indicate that stimulation-mediated Thr dephosphorylation allows decreased association of apactin with EBP50/NHERF and fosters actin remodeling to coat zymogen granules. Stimulation-mediated Ser phosphorylation increases apactin association with the actin cytoskeleton, maintaining tight bundling of actin microfilaments at the apical surface. Thus, apactin is involved in remodeling the apical cytoskeleton during regulated exocytosis in a manner controlled by phosphorylation of the apactin C-Tail.
...
PMID:Apactin is involved in remodeling of the actin cytoskeleton during regulated exocytosis. 1514 79


<< Previous 1 2 3 4 5 6 Next >>

---