u-0126 and manumycin

u-0126 has been researched along with manumycin* in 4 studies

Other Studies

4 other study(ies) available for u-0126 and manumycin

ArticleYear
Role of Ras, ERK, and Akt in glucocorticoid-induced differentiation of embryonic rat somatotropes in vitro.
    Molecular and cellular biochemistry, 2014, Volume: 391, Issue:1-2

    This study investigated the roles of Ras, ERK, and Akt in the glucocorticoid-induced differentiation of growth hormone-producing pituitary cells in vitro. Pituicytes isolated from day-18 rat embryos were cultured with 50 mM dexamethasone in addition to specific inhibitors of Ras (manumycin; 0.5, 5, 50 nM), ERK (U0126, 10 μM), or Akt (LY294002, 25 μM). Differentiation was assessed using immunofluorescent staining of intracellular growth hormone. Radioimmunoassay and Western blot analyses were used to determine levels of secreted and intracellular growth hormone, respectively. Manumycin reduced the fraction of growth hormone-positive cells and dexamethasone-induced growth hormone secretion in a dose-dependent manner (both P < 0.001). In the absence of dexamethasone, LY294002 and U0126 did not alter the fraction of growth hormone-positive cells or intracellular growth hormone protein expression or secretion. Both LY294002 and U0126 alone significantly attenuated the fraction of dexamethasone-treated GH-positive cells and the secretion of GH compared to those of cells treated only with dexamethasone (50 nM for 44 h or 48 h) (all P < 0.05). Dexamethasone treatment alone did not change GH protein levels. Treatment of cells with a combination of LY294402 and U0126 significantly attenuated the fraction of dexamethasone-treated GH-positive cells, GH protein levels, and GH secretion compared to cells treated with dexamethasone alone (all P < 0.05). Moreover, dexamethasone-induced phosphorylation of GTP-Ras, ERK, and Akt was significantly attenuated by exposure to the respective inhibitors (P < 0.05). Taken together, our results indicate that Ras, ERK, and Akt are key effectors in the glucocorticoid-induced differentiation of growth hormone-secreting cells.

    Topics: Animals; Butadienes; Cell Differentiation; Cell Survival; Chromones; Dexamethasone; Embryo, Mammalian; Extracellular Signal-Regulated MAP Kinases; Fibroblast Growth Factor 2; Glucocorticoids; Growth Hormone; Morpholines; Nitriles; Phosphorylation; Polyenes; Polyunsaturated Alkamides; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; ras Proteins; Rats, Sprague-Dawley; Somatotrophs

2014
Receptor-mediated tobacco toxicity: acceleration of sequential expression of alpha5 and alpha7 nicotinic receptor subunits in oral keratinocytes exposed to cigarette smoke.
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2008, Volume: 22, Issue:5

    Tobacco products and nicotine alter the cell cycle and lead to squamatization of oral keratinocytes (KCs) and squamous cell carcinoma. Activation of nicotinic acetylcholine receptors (nAChRs) elicits Ca(2+) influx that varies in magnitude between different nAChR subtypes. Normal differentiation of KCs is associated with sequential expression of the nAChR subtypes with increasing Ca(2+) permeability, such as alpha5-containing alpha3 nAChR and alpha7 nAChR. Exposure to environmental tobacco smoke (ETS) or an equivalent concentration of nicotine accelerated by severalfold the alpha5 and alpha7 expression in KCs, which could be abolished by mecamylamine and alpha-bungarotoxin with different efficacies, suggesting the following sequence of autoregulation of the expression of nAChR subtypes: alpha3(beta2/beta4) > alpha3(beta2/beta4)alpha5 > alpha7 > alpha7. This conjecture was corroborated by results of quantitative assays of subunit mRNA and protein levels, using nAChR-specific pharmacologic antagonists and small interfering RNAs. The genomic effects of ETS and nicotine involved the transcription factor GATA-2 that showed a multifold increase in quantity and activity in exposed KCs. Using protein kinase inhibitors and dominant negative and constitutively active constructs, we characterized the principal signaling cascades mediating a switch in the nAChR subtype. Cumulative results indicated that the alpha3(beta2/beta4) to alpha3(beta2/beta4)alpha5 nAChR transition predominantly involved protein kinase C, alpha3(beta2/beta4)alpha5 to alpha7 nAChR transition-Ca(2+)/calmodulin-dependent protein kinase II and p38 MAPK, and alpha7 self-up-regulation-the p38 MAPK/Akt pathway, and JAK-2. These results provide a mechanistic insight into the genomic effects of ETS and nicotine on KCs and characterize signaling pathways mediating autoregulation of stepwise overexpression of nAChR subtypes with increasing Ca(2+) permeability in exposed cells. These observations have salient clinical implications, because a switch in the nAChR subunit composition can bring about a corresponding switch in receptor function, leading to profound pathobiologic effects observed in KCs exposed to tobacco products.

    Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; alpha7 Nicotinic Acetylcholine Receptor; Bungarotoxins; Butadienes; Carbazoles; Conotoxins; Egtazic Acid; GATA2 Transcription Factor; Humans; Imidazoles; Indoles; Keratinocytes; Nerve Tissue Proteins; Nicotine; Nitriles; Phenols; Polyenes; Polyunsaturated Alkamides; Pyridines; Receptors, Nicotinic; RNA, Small Interfering; Signal Transduction; Smoking; Tobacco Smoke Pollution; Tyrphostins; Up-Regulation

2008
Suppression of cell spreading by v-Crk requires Ras-MEK-MAP kinase signaling.
    Oncogene, 2001, Sep-13, Volume: 20, Issue:41

    We investigated the attachment and spreading of v-Crk-transformed cells, v-Crk3Y1, on fibronectin. Transformation by v-Crk virtually suppressed the spreading, but not the attachment, of cells on fibronectin. This suppression of cell spreading was not correlated with the suppression of integrin alpha5 and beta1 expression. However, the spreading of v-Crk3Y1 on fibronectin was dramatically restored by either expression of dominant-negative Ras or treatment with manumycin A, a Ras farnesyltransferase inhibitor. Moreover, both expression of dominant-negative MEK1 and treatment of cells with U0126, a MEK1 inhibitor, restored the cell spreading of v-Crk3Y1. In contrast, neither treatment with LY294002, a PI3K inhibitor, nor expression of dominant-negative C3G showed no effect on cell spreading on fibronectin. Taken together, our results suggest that, among multiple signaling pathways activated by v-Crk, the Ras-MEK1-MAP kinase cascade plays a pivotal role in the suppression of cell spreading on fibronectin, but C3G and the PI3 kinase do not.

    Topics: Animals; Butadienes; Cell Adhesion; Cell Line; Cell Line, Transformed; Chromones; Enzyme Inhibitors; Fibronectins; Guanine Nucleotide-Releasing Factor 2; MAP Kinase Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Morpholines; Nitriles; Oncogene Protein v-crk; Phosphoinositide-3 Kinase Inhibitors; Polyenes; Polyunsaturated Alkamides; Protein Serine-Threonine Kinases; ras Proteins; Rats; Receptors, Fibronectin; Retroviridae Proteins, Oncogenic; Signal Transduction

2001
The Ras-mitogen-activated protein kinase pathway is critical for the activation of matrix metalloproteinase secretion and the invasiveness in v-crk-transformed 3Y1.
    Cancer research, 2000, May-01, Volume: 60, Issue:9

    To search for the intracellular signaling pathway critical for the secretion of matrix metalloproteinases (MMP), we studied the effects of dominant negative Ras (S17N Ras) and dominant negative MEK1 (MEK1AA) expression in v-crk-transformed 3Y1. Expression of either S17N Ras or MEK1AA dramatically suppressed the augmented secretion of MMP-2 and MMP-9 in v-crk-transfected 3Y1. Similarly, a Ras farnesyltransferase inhibitor, manumycin A, and a MEK1 inhibitor, U0126, suppressed MMP secretion in a dose-dependent manner, whereas a PI3 kinase inhibitor, wortmannin, could not. In addition, the suppression of MMP secretion by S17N Ras showed good correlation with the inhibition of in vitro invasiveness of the cells. In contrast, expression of dominant negative C3G did not suppress MMP secretion, although it substantially blocked the c-Jun N-terminal kinase activation. Taken together, the Ras-MEK1 pathway, but not the C3G-JNK pathway, seems to play a key role in the activation of MMP secretion and, hence, the invasiveness of v-crk-transformed cells.

    Topics: Androstadienes; Animals; Butadienes; Cell Line, Transformed; Collagen; Drug Combinations; Enzyme Activation; Enzyme Inhibitors; Fibroblasts; Guanine Nucleotide-Releasing Factor 2; Guanosine Diphosphate; Guanosine Triphosphate; Immunoblotting; Laminin; MAP Kinase Kinase 1; MAP Kinase Signaling System; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Mitogen-Activated Protein Kinase Kinases; Nitriles; Oncogene Protein v-crk; Polyenes; Polyunsaturated Alkamides; Protein Serine-Threonine Kinases; Proteoglycans; ras Proteins; Rats; Retroviridae Proteins, Oncogenic; Signal Transduction; src Homology Domains; Wortmannin

2000
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