Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene encoding human tissue-type plasminogen activator (t-PA) is regulated in a cell-type-specific manner. Previous studies in non-endothelial cells have indicated that basal and phorbol ester mediated induction is controlled by a cAMP response element (CRE) referred to as the tPACRE, and an activating protein 2 (AP-2)-like site. The classification of the AP-2-like site was assigned on the basis of its sequence homology, but has been shown in some cell systems to be recognised by promoter-specific transcription factor-1 (Sp-1). Here, we have investigated the transcriptional regulation of the t-PA gene in endothelial cells and addressed the functional roles of the tPACRE and the Sp-1/AP-2-like sites. 5'-RACE experiments indicate that the t-PA gene uses two transcription initiation sites in these cells with the downstream site being preferred. Functional analyses of the t-PA promoter using reporter-gene constructs transfected into C11STH endothelial cells demonstrate that the first 410 bp of the t-PA promoter confers an increase in reporter-gene activity on treatment with 4beta-phorbol 12-myristate 13-acetate (PMA). Mutagenesis of either the tPACRE or the Sp-1/AP-2 site weakens both basal and inducible expression, while disruption of both sites renders the promoter completely unresponsive. Using supershift assays, we identify the predominant tPACRE-binding proteins in nuclear extracts prepared from both C11STH cells and primary umbilical vein endothelial cells (HUVECs) as activating transcription factor 2, CREB (cAMP-responsive-element-binding protein), CREM (cAMP response element modulator) and c-jun. Treatment of cells with PMA results in a selective recruitment of jun-D to the tPACRE, while Sp-1 was identified as the major transcription factor that recognises the AP-2-like site. Based on this data and previous reports, we have reassigned this as a Sp-1-binding site. Finally, the identification of specific endothelial-derived t-PACRE-binding proteins suggests an integral role for these factors in the regulation of t-PA gene expression in human endothelial cells.
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PMID:Transcriptional regulation of the tissue-type plasminogen-activator gene in human endothelial cells: identification of nuclear factors that recognise functional elements in the tissue-type plasminogen-activator gene promoter. 985

Bungarus multicinctus (Taiwan banded krait) beta-bungarotoxins consist of two dissimilar polypeptide chains, A and B. The A chain is structurally homologous to phospholipase A(2) (PLA(2)) enzymes. The structural organization of the genes encoding A1, A2 and A8 chains are reported in this study. Their nucleotide sequences shared up to 97.5% identity. Alignment of the determined A chain genes with their cDNAs revealed that A1 chain gene organized with four exons and three introns, while A2 chain gene comprised three exons and two introns. When A2 chain is expressed, the region corresponding to the first exon of A1 chain gene is skipped instead of the inclusion of intronic sequence adjacent to the second exon. The resulting A2 chain mRNA encoded a 25 residue signal peptide, which is different from A1 chain mRNA with a 27 residue signal peptide. Nevertheless, expression of the A chain genes was partly regulated by a common mechanism as evidenced by sequence conservation of their promoter region and consensus transcriptional factor binding-sites inside this region. 5'-RACE analyses revealed that A chain mRNAs with 27 residue signal peptide represented the predominant species in the preparation of B. multicinctus venom gland mRNAs. Comparative analyses on PLA(2) genes and cDNAs suggest that this is the first report on the skipping of exon which changes the signal peptide sequence of snake venom proteins.
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PMID:The organization of the genes encoding the A chains of beta-bungarotoxins: evidence for the skipping of exon. 1236 13

Eicosanoids are oxygenated C20 polyunsaturated fatty acids that mediate various physiological processes in insects. Eicosanoid biosynthesis begins with a C20 precursor, arachidonic acid (5,8,11,14-eicosatetraenoic acid: AA). AA is usually released from phospholipids at sn-2 position by catalytic activity of phospholipase A2 (PLA2). Although various PLA2s classified into 16 gene families (= Groups) are known in various biological systems, few PLA2s are known in insects. Only two PLA2s involved in intracellular calcium independent PLA2 (iPLA2) group have been identified in lepidopteran insects with well known eicosanoid physiology. This study reports the first secretory PLA2 (sPLA2) in lepidopteran insects. A partial open reading frame (ORF) of PLA2 was obtained by interrogating Spodoptera exigua transcriptome. Subsequent 3'-RACE resulted in a full ORF (Se-sPLA2A) encoding 194 amino acid sequence containing signal peptide, calcium-binding domain, and catalytic site. Phylogenetic analysis indicated that Se-sPLA2A was clustered with other Group III sPLA2s. Se-sPLA2A was expressed in most larval instars except late last instar. Its expression was inducible by immune challenge and juvenile hormone analog injection. RNA interference of Se-sPLA2A significantly suppressed cellular immunity and impaired larval development. These results suggest that non-venomous sPLA2 plays a crucial role in immune and developmental processes in S. exigua, a lepidopteran insect.
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PMID:A non-venomous sPLA2 of a lepidopteran insect: Its physiological functions in development and immunity. 3010 51