Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both erythropoietin (EPO) and the short-form thrombopoietin (TPO) were expressed at low levels whereas the long-form TPO was expressed at high levels in transgenic animals. To elucidate the role of carboxy-terminal half of the long-form TPO which is absent in the short-form, we generated recombinant TPO or EPO expression vectors which contain or lack the carboxy-terminal half of TPO and examined their expression in the HC11 and 293 cells. The long-form TPO was expressed higher than the short-form regardless of the cell types, transfection modes, and promoters. When 3'-half of the long-form TPO cDNA was placed downstream of the EPO cDNA to act as a 3'-untranslated region, expression of EPO was moderately increased at the RNA level, however, no remarkable increase was observed at the protein level. These results suggest that the low expression of EPO, as like as the short-form TPO, is due to absence of the 3'-half in the full-length TPO that confers stability both at the RNA and protein levels.
Mol Cells 2005 Apr 30
PMID:3'-Half of the thrombopoietin cDNA confers higher expression of erythropoietin at the RNA level but not at the protein level. 1587 2

Cholera toxin (CT) is the causative agent of cholera, binds to GM1 glycosphingolipids, induces the production of cellular cAMP and is also a very powerful mucosal adjuvant. Although the mechanism of the CT induction of cAMP production is well understood, molecular mechanisms of the adjuvanticity of cholera toxin are yet to be delineated. Here, we examined the interaction of CT with human lymphocytes and monocytes by analyzing the host transcriptional profiles using cDNA arrays. The time courses of the transcriptional activations and repressions of affected genes in lymphocytes and monocytes in response to cholera toxin were determined. CT induced the expression of IL-8 and MIP-1 early in the CT exposure. VEGF, TIMP1, HIF-1alpha, MMP11, hek 8, MCP1, IL-6, GCP 2, urokinase plasminogen activator, and TNF-alpha receptor were upregulated after 4h CT treatment. These genes showed increased expression for 48 h. MRP-14, MRP-8A increased expression after 16 h CT treatment. RT-PCR and real-time PCR using cDNA specific primers confirmed the CT induction and repression of selected genes. The results suggest that immunomodulatory genes were among the genes that were affected the most by CT, and induction of these genes may contribute to the CT adjuvanticity.
Mol Immunol 2006 Mar
PMID:Induction of immunomodulator transcriptional responses by cholera toxin. 1602 26

Hypoxia, a common consequence of solid tumor growth in breast cancer or other cancers, serves to propagate a cascade of molecular pathways which include angiogenesis, glycolysis, and various cell-cycle control proteins. As we have shown previously, hypoxia activates STAT5 (signal transducer and activator of transcription 5) and increases its binding activity to the GAS element in mammary epithelial cells. In this study we attempted to elucidate the mechanism by which cyclin D1 is regulated by the STAT5 protein under hypoxic conditions. Our data demonstrate that hypoxia (2% O(2)) or desferrioxamine (DFO) induces tyrosine and serine phosphorylation of STAT5 in human breast cancer cells (MCF-7) and mammary epithelial cells (HC11). Imunoprecipitation and subsequent Western analysis showed that Jak2 leads to the tyrosine phosphorylation and activation of STAT5a or STAT5b under hypoxic conditions. Using a transfected COS-7 cell model system, we demonstrate that the activity of a cyclin D1 promoter-luciferase construct increased under hypoxic conditions or DFO treatment. The activity of the STAT5b/cyclin D1 promoter increased significantly by 12 h of hypoxia, whereas the activity of the STAT5a/cyclin D1 promoter was unaffected under hypoxic conditions. These increases in promoter activity are predominantly mediated by the Jak2/STAT5b signaling pathway. We have shown by EMSA that hypoxia induces STAT5 to bind to the cyclin D1 promoter (GAS-1) in MCF-7 and HC11 cells. These data suggest that STAT5b may mediate the transcriptional activation of cyclin D1 after hypoxic stimulation.
Exp Mol Med 2005 Aug 31
PMID:Hypoxia activates the cyclin D1 promoter via the Jak2/STAT5b pathway in breast cancer cells. 1615 12

Acrylonitrile is a very high volume industrial chemical used primarily in the manufacture of plastics and rubber, which displays a pronounced acute toxicity and may be carcinogenic. The damage to the hematopoietic function by acrylonitrile may result from interference with cytokine production and cytokine receptor binding. Our present data show that acrylonitrile modulates the expression of some genes implicated in cell differentiation, cell-cycle progression, and clonogenic potential of human cord blood cells. A macroarray hybridization analysis showed that expression of the CXCR4, MCP-1, and MRP8 genes was modified by acrylonitrile exposure. Moreover, the acrylonitrile cell target seems to be the myeloid compartment, as assessed by a CFU-GM assay. In particular, the downregulation of CXCR4, MCP1, and MRP8 can be responsible for the observed reduction of cell proliferation and clonogenic capability of CFU-GM precursors. A Western blot assay showed an acrylonitrile-dependent induction of Bax, while Bcl-2 expression changed only after 48 h of chemical exposure. Bax was overexpressed in respect to Bcl-2, and this fact can be responsible for the induction in cell death after 24 h of treatment. C-fos and c-jun were also downregulated after 24 h and 6 h of treatment, respectively.
J Biochem Mol Toxicol 2005
PMID:Gene and protein expressions in human cord blood cells after exposure to acrylonitrile. 1617 56

The G protein-coupled receptor kinase 2 (GRK2) phosphorylates and desensitizes ligand-activated G protein-coupled-receptors. Here, evidence is shown for a novel role of GRK2 in regulating chemokine-mediated signals. The presence of increased levels of GRK2 in human embryonic kidney (HEK) 293 cells produced a significant reduction of the extracellular signal-regulated kinase (ERK) response to CCL2. This effect is independent of its role in receptor phosphorylation because the kinase-deficient mutant GRK2K220R was able to reduce this response, and ERK activation by CCR2BIX, a phosphorylation-defective receptor mutant, was also inhibited by GRK2. Constructs containing the Galpha(q)-binding RGS-like RH domain of GRK2 or its Gbetagamma-binding domain could not reproduce the inhibition, thus revealing that GRK2 acts downstream of G proteins. Interestingly, chemokine-driven mitogen-activated protein kinase kinase (MEK) stimulation is not affected in cells overexpressing GRK2 or GRK2K220R or in splenocytes from heterozygous GRK2 mice, where reduced kinase levels correlate with enhanced ERK activation by chemokines. We find GRK2 and MEK in the same multimolecular complex, thus suggesting a mechanism for GRK2 regulation of ERK activity that involves a direct or coordinate interaction with MEK. These results suggest an important role for GRK2 in the control of chemokine induction of ERK activation at the level of the MEK-ERK interface.
Mol Biol Cell 2006 Jan
PMID:G protein-coupled receptor kinase 2 negatively regulates chemokine signaling at a level downstream from G protein subunits. 1622 91

Ozone exposure produces acute inflammation and neutrophil influx in the distal lung. Alveolar epithelial cells cover a large surface area, secrete chemokines, and may initiate or modify the inflammatory response. The effect of ozone on chemokine production by these cells has not been defined. Isolated rat type II cells were cultured in different conditions to express the morphologic appearance and biochemical markers for the type I and the type II cell phenotypes. These cells were exposed to ozone at an air/liquid interface. The type I-like cells were more susceptible to injury than the type II cells and showed signs of injury at exposure levels of 100 ppb ozone for 60 min. Both phenotypes showed evidence of lipid peroxidation after ozone exposure as measured by 8-isoprostane production, but neither phenotype secreted increased amounts of MIP-2 (CXCL3), CINC-1 (CXCL1), or MCP-1 (CCL2) in response to ozone. Both cell phenotypes secreted MIP-2 and MCP-1 in response to IL-1beta or lipopolysaccharide, but there was no priming or synergy with ozone. It is likely that the inflammatory response to ozone in the alveolar compartment is not due to the direct effect of ozone on epithelial cells.
Am J Respir Cell Mol Biol 2006 Feb
PMID:Alveolar epithelial cells secrete chemokines in response to IL-1beta and lipopolysaccharide but not to ozone. 1623 43

To investigate apoptosis in HC11 mammary epithelial cells, we compared the gene expression profiles of actively growing and serum-starved apoptotic cells using a mouse apoptosis gene array and 33P-labeled cDNA prepared from the RNA of the two cultures. Analysis of the arrays showed that expression of several genes such as clusterin, secreted frizzled related protein mRNA (sFRP-1), CREB-binding protein (CBP), and others was higher in the apoptotic cells whereas expression of certain genes including survivin, cell division cycle 2 homolog A (CDC2), and cyclin A was lower. These expression patterns were confirmed by RT-PCR and/or Northern analyses. We compared the expression of some of these genes in the mouse mammary gland under various physiological conditions. The expression levels of genes (clusterin, CBP, and M6P-R) up-regulated in apoptotic conditions were higher at involution than during lactation. On the other hand, genes (Pin, CDC2) downregulated in apoptotic conditions were relatively highly expressed in virgin and pregnant mice. We conclude that certain genes such as clusterin, sFRP-1, GAS1 and CBP are induced in apoptotic mammary epithelial cells, and others are repressed. Moreover, the apoptosis array is an efficient technique for comparing gene expression profiles in different states of the same cell type.
Mol Cells 2005 Aug 31
PMID:Expression profiles of apoptosis genes in mammary epithelial cells. 1625 47

The human herpes virus 6 (HHV-6)-encoded chemokine receptor U51 constitutively activates phospholipase C (PLC) and inhibits cAMP-responsive element (CRE)-mediated gene transcription via the activation of G(q/11) proteins. Yet, chemokines known to bind U51 differentially regulate U51 coupling to G proteins. CCL5/RANTES induced pertussis toxin (PTX)-insensitive increases in PLC activity and changes in intracellular free calcium concentration ([Ca2+]i), whereas both CCL2/MCP-1 and CCL11/eotaxin failed to stimulate PLC activity or increase [Ca2+]i. In contrast, all three chemokines counteracted the effects of U51 on CRE activity via the activation of PTX-sensitive G(i/o) proteins. For each of the tested chemokines, coexpression of U51 with a variety of G alpha subunits, however, revealed a distinct profile for preferred G-protein coupling, which could be shifted by modulation of the relative expression of G proteins. These findings are consistent with a chemokine-selective trafficking of receptor stimulus to distinct G proteins and suggest that the constitutive activity of U51 and the chemokine-induced signaling involve different active states of the receptor. By virtue of its ability to constitutively activate signaling pathways, its G-protein promiscuity, and the chemokine-directed trafficking of receptor stimulus, U51 can be considered a sensitive and versatile virally encoded signaling device, potentially of importance in HHV-6-related pathologies.
Mol Pharmacol 2006 Mar
PMID:Chemokine-directed trafficking of receptor stimulus to different g proteins: selective inducible and constitutive signaling by human herpesvirus 6-encoded chemokine receptor U51. 1633 87

We tested the hypothesis that cholinergic stimulation and cyclic stretch regulate inflammatory gene expression in intact airway smooth muscle by measuring mRNA expression in bovine tracheal smooth muscle using limited microarray analysis and RT-PCR. Carbachol (1 microM) induced significant increases in the expression of cyclooxygenase (COX)-1, COX-2, IL-8, and plasminogen activator, urokinase type (PLAU) to levels ranging from 1.3- to 3.1-fold of control. Sinusoidal length oscillation at an amplitude of 10% muscle length and a frequency of 1 Hz induced significant increases in the expression of CCL-2, COX-2, IL-1 beta, and IL-6 to levels ranging from 12- to 206-fold of control. Decreasing the oscillatory amplitude by 50% did not significantly change inflammatory gene expression. In contrast, decreasing the oscillatory frequency by 50% significantly attenuated inflammatory gene expression by 76-93%. Nifedipine (1 microM) had an insignificant effect on carbachol-induced gene expression, but significantly inhibited sinusoidal length oscillation-induced inflammatory gene expression by 40-78%. Correlation analysis revealed two groups of genes with differential responses to sinusoidal length oscillation. The highly responsive group included COX-2, IL-6, and IL-8, which exhibited 45- to 364-fold increases in gene expression in response to sinusoidal length oscillation. The moderately responsive group included CCL2 and PLAU, which exhibited 13- to 19-fold increases in gene expression in response to sinusoidal oscillation. These findings suggest that cyclic stretch regulates inflammatory gene expression in intact airway smooth muscle in an amplitude- and frequency-dependent manner by modulating the activity of L-type voltage-gated calcium channels.
Am J Respir Cell Mol Biol 2006 Apr
PMID:Cholinergic receptor and cyclic stretch-mediated inflammatory gene expression in intact ASM. 1633 98

To glean biological differences and similarities of peripheral T-cell lymphoma-not otherwise specified [PTCL-NOS] to diffuse large B-cell lymphoma (DLBCL), a transcriptosome analysis was done on five PTCL-NOS and four DLBCL patients and validated by quantitative real-time reverse transcription-PCR on 10 selected genes. Normal peripheral blood T cells, peripheral blood B cells, and lymph node were used as controls. The resultant gene expression profile delineated distinct "tumor profile signatures" for PTCL-NOS and DLBCL. Several highly overexpressed genes in both PTCL-NOS and DLBCL involve the immune network, stroma, angiogenesis, and cell survival cascades that make important contributions to lymphomagenesis. Inflammatory chemokines and their receptors likely play a central role in these complex interrelated pathways: CCL2 and CXCR4 in PTCL-NOS and CCL5 and CCR1 in DLBCL. Highly overexpressed oncogenes unique to PTCL-NOS are SPI1, STK6, alpha-PDGFR, and SH2D1A, whereas in DLBCL they are PIM1, PIM2, LYN, BCL2A1, and RAB13. Oncogenes common to both lymphomas are MAFB, MET, NF-kappaB2, LCK, and LYN. Several tumor suppressors are also down-regulated (TPTE, MGC154, PTCH, ST5, and SUI1). This study illustrates the relevance of tumor-stroma immune trafficking and identified potential novel prognostic markers and targets for therapeutic intervention.
Mol Cancer Ther 2005 Dec
PMID:Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures. 1637 2


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