Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of alpha1 adrenergic receptors not only stimulates smooth muscle contraction but also modifies gene expression. We wondered if alpha1 adrenergic receptors could activate transcription of genes regulated by the cAMP response element-binding protein (CREB). Using Rat1 cells stably transfected with each of the three cloned human alpha1 adrenergic receptor subtypes, norepinephrine strongly stimulated CREB phosphorylation in alpha1A and alpha1B but more weakly in alpha1D-transfected cells. Norepinephrine increased the activity of a somatostatin cAMP-regulated enhancer-chloramphenicol acetyltransferase reporter in these cells. alpha1 adrenergic receptors are known to activate protein kinase C (PKC) and increase [Ca2+ ]i. Nonetheless, neither GF109203X, a PKC inhibitor, nor BAPTA-AM, a calcium chelator, blocked phosphorylation of CREB induced by norepinephrine. In addition, alpha1 adrenergic receptor-induced CREB phosphorylation was not mediated via the mitogen-activated protein kinase pathway because norepinephrine did not stimulate mitogen-activated protein kinase activity in these cells. Activation of alpha1 adrenergic receptors increased cAMP accumulation in these cells. Norepinephrine-induced cAMP-regulated enhancer-chloramphenicol acetyltransferase activity was inhibited either by expression of the PKA inhibitory peptide or a dominant negative PKA regulatory subunit mutant. These results demonstrate that alpha1 adrenergic receptors activate the transcription factor CREB by a PKA-dependent pathway.
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PMID:Phosphorylation of the cAMP response element-binding protein and activation of transcription by alpha1 adrenergic receptors. 979 25

cAMP increases transcription of the mitochondrial (mit.) gene for 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase, which encodes an enzyme that has been proposed as a control site of ketogenesis. The incubation of Caco-2 cells with cAMP increased mit.HMG-CoA synthase mRNA levels 4-fold within 24 h. We have identified an active cAMP-response element (CRE) located 546 bp upstream of the mit. HMG-CoA synthase promoter that is necessary for the induction of expression by dibutyryl cAMP. Co-transfections of constructs, containing the CRE element of the mit.HMG-CoA synthase promoter fused to the gene for chloramphenicol acetyltransferase, with protein kinase A and a dominant-negative mutant of cAMP-response-element-binding protein (CREB) show that the response to cAMP is mediated by the transcription factor CREB. The CRE element confers responsiveness of protein kinase A to a heterologous promoter in transfection assays in Caco-2 cells. Gel-retardation assays revealed that the mit.HMG-CoA synthase CRE binds to recombinant CREB. The shifted band obtained with the putative mit. HMG-CoA synthase CRE sequence and nuclear proteins from Caco-2 cells competed with CRE sequences of other genes such as somatostatin and phosphoenolpyruvate carboxykinase. We conclude that the regulation of the expression of the gene for mit.HMG-CoA synthase in Caco-2 cells by cAMP is mediated by a CRE sequence in the promoter.
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PMID:Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase promoter contains a CREB binding site that regulates cAMP action in Caco-2 cells. 1062 Apr 95


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