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)

Recruitment to activated tyrosine kinase growth factor receptors of Grb2 and p21(ras) leads to downstream activation of the kinases Raf, MAPK/Erk kinase (Mek) and, subsequently, extracellular signal-regulated kinase (Erk). Activated Erk phosphorylates specific serine residues within cytosolic phospholipase A(2) (PLA(2)), promoting enzyme translocation to membranes and facilitating liberation of arachidonic acid (AA). In the A549 human adenocarcinoma cell line dexamethasone inhibited epidermal growth factor (EGF)-stimulated cytosolic PLA(2) (cPLA(2)) activation and AA release by blocking the recruitment of Grb2 to the activated EGF receptor (EGF-R) through a glucocorticoid receptor (GR)-dependent (RU486-sensitive), transcription-independent (actinomycin-insensitive), mechanism. The dexamethasone-induced block of Grb2 recruitment was parallelled by changes in phosphorylation status and subcellular localization of lipocortin 1 (LC1) and an increase in the amount of the tyrosine phosphoprotein co-localized with EGF-R. Like dexamethasone, peptides containing E-Q-E-Y-V from the N-terminal domain of LC1 also blocked ligand-induced association of Grb2, p21(ras) and Raf. Our results point to an unsuspected rapid effect of glucocorticoids, mediated by occupation of GR but not by changes in gene transcription, which is brought about by competition between LC1 and Grb2 leading to a failure of recruitment off signalling factors to EGF-R
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PMID:Glucocorticoids act within minutes to inhibit recruitment of signalling factors to activated EGF receptors through a receptor-dependent, transcription-independent mechanism. 1080 65

We have studied the induction of cyclooxygenase-2 (COX-2) in macrophages consequent to ligating the alpha(2)-macroglobulin (alpha(2)M) signalling receptor (alpha(2)MSR) with receptor-recognized forms of alpha(2)M (alpha(2)M*). Macrophage stimulation with alpha(2)M* increased total cellular and nuclear COX-2 two- to threefold. The maximal increase in COX-2 occurred at a ligand concentration of 50-100 pM and after 2 h. Modulation of intracellular Ca(2+) levels or incubation of [35S] methionine-labelled macrophages with actinomycin D, prior to treatment with alpha(2)M*, markedly reduced the induction of total cellular and nuclear COX-2. Protein kinase C (PKC) or phospholipase A(2) (PLA(2)) inhibition in alpha(2)M*-stimulated macrophages or inhibition of the p21(ras)-dependent mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI 3-kinase) signalling pathways also significantly reduced alpha(2)M*-induced total cellular and nuclear COX-2 expression. Thus, COX-2 induction is dependent on cPLA(2) activity, Ca(2+) mobilization, and PKC activity and requires participation of both the p21(ras)-dependent MAPK and PI 3-kinase signalling pathways. COX-2 activation may mediate alpha(2)M*-induced mitogenesis, which we have previously observed in this and other cell types.
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PMID:Induction of cyclooxygenase-2 synthesis by ligation of the macrophage alpha(2)-macroglobulin signalling receptor. 1158 15

Gene expression of cytosolic phospholipase A(2) (cPLA(2)) and protein level of secretory PLA(2) group X (sPLA(2)-X) are upregulated in human colorectal cancer and provide cyclooxygenase-2 (COX-2) with arachidonic acid, resulting in increased levels of PGE(2). Mutated ras-genes are suggested to be involved in the regulatory pathway of cPLA(2) in lung cancer cells. We analysed the gene expression of cPLA(2) and sPLA(2)-X in 42 and 38 primary colorectal tumours, respectively, with and without K-ras mutations. We found an up-regulation of cPLA(2) mRNA but the induction in tumour tissues does not correlate with Ras-gene mutations. Moreover, our results cannot consistently reflect an overexpression of sPLA(2)-X gene in colorectal cancer tissues.
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PMID:Expression of cytosolic and group X secretory phospholipase A(2) genes in human colorectal adenocarcinomas. 1204 63

Hydroquinone (HQ) is a rodent carcinogen and a potential human carcinogen. Glutathione conjugation of HQ enhances its biological reactivity, and 2,3,5-tris-(glutathion-S-yl)hydroquinone (TGHQ) is a potent nephrotoxicant and nephrocarcinogen in the Eker rat. Moreover, a single exposure of primary epithelial cells derived from Eker rat kidneys to TGHQ transforms these cells into an immortalized phenotype (quinol-thioether transformed rat renal epithelial (QT-RRE) cells). The Eker rat bears a mutation in one allele of the tuberous sclerosis-2 (Tsc-2) tumor suppressor gene, which predisposes the animals to the development of spontaneous and chemical-induced renal cell carcinoma. Thus, the Eker rat provides a unique model for elucidating the mechanisms of renal tubular epithelial carcinogeneisis. cDNA microarray analysis of QT-RRE3 cells and of tumor tissue derived from the kidneys of Eker rats treated with TGHQ revealed alterations (by threefold or greater) in the expression of a total of 80 genes. Fifteen percent of these genes exhibited similar expression patterns in both QT-RRE cells and tumor tissue. The differentially expressed genes primarily participate in three major areas: (1) signal transduction or in the regulation of signal transduction (extracellular signal regulated kinase 2 (ERK2); protein kinase CK2; protein kinase B; c-jun; NF-kappaB; ras-related GTPases; annexins), (2) stress response, tissue remodeling, and DNA repair (glutathione-S-transferases; procollagen c proteinase enhancer; plasminogen activator; tissue inhibitor of metalloprotease 3; apurinic/apyrimidic endonuclease), and (3) electron transport and energy homeostasis (cytochrome c oxidase subunits). The changes in the expression of many of these genes was confirmed by reverse transcription (RT)-polymerase chain reactions (PCR) using primers specific for the differentially expressed genes. As an example, the annexin I and II genes, implicated in signal transduction, were highly induced in tumor tissue and also in dysplastic lesions isolated from the kidneys of rats treated chronically with TGHQ. The annexin I and II proteins were also upregulated in tumor tissue, which probably play an important role in TGHQ-induced nephrocarcinogenesis. Moreover, in the present study, a tumorigenicity assay using athymic nude mice revealed that QT-RRE cell lines formed tumors when injected in the subcutis of nude mice, providing evidence that the cells are malignantly transformed. Histopathological analysis further indicated that the tumors were composed of neoplastic cells, resembling renal carcinoma cells with varying degrees of atypia, with the presence of apoptotic and mitotic figures.
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PMID:Changes in gene expression during chemical-induced nephrocarcinogenicity in the Eker rat. 1458 99

Blattella germanica densovirus (BgDNV) is an autonomous parvovirus that infects the German cockroach. BgDNV possesses three mRNAs for NS proteins, two of which are splice variants of the unspliced transcript. The unspliced variant encodes open reading frame 5 (ORF5) (NS3), while NSspl1 encodes ORF3 (NS1) and ORF4 (NS2) and NSspl2 encodes the C-proximal half of NS1. BgDNV possesses three VP transcripts, one of which (VP) is unspliced, while the other two (VPspl1 and VPspl2) are generated by alternative splicing. The unspliced VP transcript contains both ORF1 and ORF2, while in VPspl1, ORF1 and ORF2 are joined in frame. The transcription of NS genes begins at an earlier stage of the virus life cycle than the transcription of VP genes. NS and VP transcripts overlap by 48 nucleotides (nt). BgDNV is characterized by two additional NS transcripts overlapping by more than 1,650 nt with VP-coding transcripts. Four different bands (97, 85, 80, and 57 kDa) corresponding to three BgDNV capsid proteins were detected on SDS-PAGE. Mass spectrometry analysis showed that the amino acid composition of the 85-kDa and 80-kDa proteins is the same. Moreover, both of these proteins are ubiquitinated. The BgDNV PLA(2) domain, which is critical for cellular uptake of the virus, is located in ORF2 and is present only in VP1. In contrast to all of the parvoviruses studied in this respect, VP2 has a unique N terminus that is not contained within VP1 and VP3. In situ recognition with NS1- and VP-specific antibodies revealed an uneven pattern of NS1 expression resembling a halo within the nuclear membrane.
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PMID:Expression strategy of densonucleosis virus from the German cockroach, Blattella germanica. 2190 Jan 60


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