Matches in Nanopublications for { ?s <http://www.w3.org/ns/prov#value> ?o ?g. }
- _6 value "LPS + IFNγ caused an increase in monolayer permeability, induction of iNOS and NADPH oxidase type 1 (Nox1) proteins, formation of superoxide, nitric oxide and 3-nitrotyrosine, and increase in PP2A activity in endothelial cells. These effects of LPS + IFNγ were diminished by tripterine (50-200 nM)." provenance.
- _7 value "LPS + IFNγ caused an increase in monolayer permeability, induction of iNOS and NADPH oxidase type 1 (Nox1) proteins, formation of superoxide, nitric oxide and 3-nitrotyrosine, and increase in PP2A activity in endothelial cells. These effects of LPS + IFNγ were diminished by tripterine (50-200 nM)." provenance.
- _7 value "Further, LPS + IFNγ -induced expression of iNOS and Nox1 was attenuated by the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor PD98059, the JNK inhibitor SP600125, the Jak2 inhibitor AG490 and the NFκB inhibitor MG132, but not by the p38 mitogen-activated protein kinase inhibitor SB203580. LPS + IFNγ stimulated phosphorylation of ERK, JNK and Jak2, and degradation of IκB, but only Jak2 phosphorylation was sensitive to tripterine (50-200 nM). Further, tripterine diminished the increased vascular permeability in inflamed air pouches." provenance.
- _5 value "Further, LPS + IFNγ -induced expression of iNOS and Nox1 was attenuated by the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor PD98059, the JNK inhibitor SP600125, the Jak2 inhibitor AG490 and the NFκB inhibitor MG132, but not by the p38 mitogen-activated protein kinase inhibitor SB203580. LPS + IFNγ stimulated phosphorylation of ERK, JNK and Jak2, and degradation of IκB, but only Jak2 phosphorylation was sensitive to tripterine (50-200 nM). Further, tripterine diminished the increased vascular permeability in inflamed air pouches." provenance.
- _7 value "Further, LPS + IFNγ -induced expression of iNOS and Nox1 was attenuated by the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor PD98059, the JNK inhibitor SP600125, the Jak2 inhibitor AG490 and the NFκB inhibitor MG132, but not by the p38 mitogen-activated protein kinase inhibitor SB203580. LPS + IFNγ stimulated phosphorylation of ERK, JNK and Jak2, and degradation of IκB, but only Jak2 phosphorylation was sensitive to tripterine (50-200 nM). Further, tripterine diminished the increased vascular permeability in inflamed air pouches." provenance.
- _7 value "Further, LPS + IFNγ -induced expression of iNOS and Nox1 was attenuated by the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor PD98059, the JNK inhibitor SP600125, the Jak2 inhibitor AG490 and the NFκB inhibitor MG132, but not by the p38 mitogen-activated protein kinase inhibitor SB203580. LPS + IFNγ stimulated phosphorylation of ERK, JNK and Jak2, and degradation of IκB, but only Jak2 phosphorylation was sensitive to tripterine (50-200 nM). Further, tripterine diminished the increased vascular permeability in inflamed air pouches." provenance.
- _7 value "Further, LPS + IFNγ -induced expression of iNOS and Nox1 was attenuated by the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor PD98059, the JNK inhibitor SP600125, the Jak2 inhibitor AG490 and the NFκB inhibitor MG132, but not by the p38 mitogen-activated protein kinase inhibitor SB203580. LPS + IFNγ stimulated phosphorylation of ERK, JNK and Jak2, and degradation of IκB, but only Jak2 phosphorylation was sensitive to tripterine (50-200 nM). Further, tripterine diminished the increased vascular permeability in inflamed air pouches." provenance.
- _6 value "Further, LPS + IFNγ -induced expression of iNOS and Nox1 was attenuated by the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor PD98059, the JNK inhibitor SP600125, the Jak2 inhibitor AG490 and the NFκB inhibitor MG132, but not by the p38 mitogen-activated protein kinase inhibitor SB203580. LPS + IFNγ stimulated phosphorylation of ERK, JNK and Jak2, and degradation of IκB, but only Jak2 phosphorylation was sensitive to tripterine (50-200 nM). Further, tripterine diminished the increased vascular permeability in inflamed air pouches." provenance.
- _6 value "Further, LPS + IFNγ -induced expression of iNOS and Nox1 was attenuated by the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor PD98059, the JNK inhibitor SP600125, the Jak2 inhibitor AG490 and the NFκB inhibitor MG132, but not by the p38 mitogen-activated protein kinase inhibitor SB203580. LPS + IFNγ stimulated phosphorylation of ERK, JNK and Jak2, and degradation of IκB, but only Jak2 phosphorylation was sensitive to tripterine (50-200 nM). Further, tripterine diminished the increased vascular permeability in inflamed air pouches." provenance.
- _5 value "The increased endothelial permeability induced by LPS + IFNγ was attenuated by the NADPH oxidase inhibitor apocynin (250 µM; based on Coyle and Kader, 2007), iNOS inhibitor 1400W (50 µM; based on Hortelano et al., 2000), and tripterine (50 nM and 200 nM; based on Allison et al., 2001) (Figure 1B). Neither apocynin, 1400W nor tripterine (50 nM and 200 nM) altered the endothelial permeability in the absence of a pro-inflammatory stimulus (Figure 1B)." provenance.
- _6 value "The increased endothelial permeability induced by LPS + IFNγ was attenuated by the NADPH oxidase inhibitor apocynin (250 µM; based on Coyle and Kader, 2007), iNOS inhibitor 1400W (50 µM; based on Hortelano et al., 2000), and tripterine (50 nM and 200 nM; based on Allison et al., 2001) (Figure 1B). Neither apocynin, 1400W nor tripterine (50 nM and 200 nM) altered the endothelial permeability in the absence of a pro-inflammatory stimulus (Figure 1B)." provenance.
- _4 value "Our previous study identified NADPH oxidase activity as the principal source of superoxide in LPS + IFNγ-stimulated microvascular endothelial cells (Wu et al., 2007; 2008)." provenance.
- _4 value "Nox1 is a catalytic subunit of NADPH oxidase that is expressed in endothelial cells (Sorescu et al., 2004; Wu et al., 2008)." provenance.
- _5 value "iNOS-derived NO and NADPH oxidase-derived superoxide react to form peroxynitrite that can nitrate the tyrosine residues of target proteins, leading to the formation of 3-nitrotyrosine." provenance.
- _4 value "Constitutive Akt/protein kinase B (PKB) activity was demonstrated in 16 of 17 cell lines by maintenance of S473 phosphorylation with serum deprivation. Additional analysis of five of 2these NSCLC lines revealed that phosphorylation of S473 and T308 correlated with in vitro kinase activity." provenance.
- _4 value "Constitutive Akt/protein kinase B (PKB) activity was demonstrated in 16 of 17 cell lines by maintenance of S473 phosphorylation with serum deprivation. Additional analysis of five of 2these NSCLC lines revealed that phosphorylation of S473 and T308 correlated with in vitro kinase activity." provenance.
- _4 value "Akt/PKB activation was phosphatidylinositol 3-kinase-dependent and promoted survival because the phosphatidylinositol 3 inhibitors LY294002 and wortmannin inhibited Akt/PKB phosphorylation, Akt/PKB activity, and increased apoptosis only in cells with active Akt/PKB." provenance.
- _6 value "Akt/PKB activation was phosphatidylinositol 3-kinase-dependent and promoted survival because the phosphatidylinositol 3 inhibitors LY294002 and wortmannin inhibited Akt/PKB phosphorylation, Akt/PKB activity, and increased apoptosis only in cells with active Akt/PKB." provenance.
- _5 value "Phosphorylation patterns for T308, the PDK1 site (Fig. 1B), generally correlated with the S473 pattern; only the H1155, H157, and H1703 cells displayed phosphorylation of Akt/PKB at T308." provenance.
- _3 value "Phosphorylation patterns for T308, the PDK1 site (Fig. 1B), generally correlated with the S473 pattern; only the H1155, H157, and H1703 cells displayed phosphorylation of Akt/PKB at T308." provenance.
- _3 value "Phosphorylation patterns for T308, the PDK1 site (Fig. 1B), generally correlated with the S473 pattern; only the H1155, H157, and H1703 cells displayed phosphorylation of Akt/PKB at T308." provenance.
- _4 value "we tested the ability of two PI3-K inhibitors, LY294002 and wortmannin, to inhibit Akt/PKB phosphorylation. Fig. 2A shows that both LY294002 and wortmannin completely inhibited phosphorylation of S473 in the three NSCLC cell lines that maintain S473 phosphorylation under serum deprivation. Native Akt/PKB levels did not change. Similar results were obtained for T308 phosphorylation (Fig. 2B)." provenance.
- _4 value "we tested the ability of two PI3-K inhibitors, LY294002 and wortmannin, to inhibit Akt/PKB phosphorylation. Fig. 2A shows that both LY294002 and wortmannin completely inhibited phosphorylation of S473 in the three NSCLC cell lines that maintain S473 phosphorylation under serum deprivation. Native Akt/PKB levels did not change. Similar results were obtained for T308 phosphorylation (Fig. 2B)." provenance.
- _4 value "we tested the ability of two PI3-K inhibitors, LY294002 and wortmannin, to inhibit Akt/PKB phosphorylation. Fig. 2A shows that both LY294002 and wortmannin completely inhibited phosphorylation of S473 in the three NSCLC cell lines that maintain S473 phosphorylation under serum deprivation. Native Akt/PKB levels did not change. Similar results were obtained for T308 phosphorylation (Fig. 2B)." provenance.
- _5 value "These data demonstrate that Akt/PKB phosphorylation in the three positive cell lines is PI3-K-dependent, making it unlikely that other kinases are directly involved in activating Akt/PKB." provenance.
- _6 value "we transiently cotransfected NSCLC cell lines with HA-tagged dominant negative Akt/PKB (K179M Akt/PKB) and GFP and assessed apoptosis in the GFP-positive cells. Fig. 6 shows that in the cell lines with high Akt/PKB activity, transfection of K179M Akt/PKB resulted in a 2–5-fold increase in basal apoptosis." provenance.
- _4 value "thrombospondin-1 binds to the platelet membrane and mediates adhesion" provenance.
- _6 value "To study the role of αv in the formation of the RTK-integrin complex, we transfected PDGF-Rβ into CHO cells that overexpress the platelet integrin αIIbβ3. As shown in Fig. 5A, equal amounts of PDGF-Rb were coprecipitated with both anti-αIIb and anti-β3 antibodies." provenance.
- _9 value "We have previously shown that the attachment of cells to a substrate through the αvβ3 integrin enhances the ability of insulin and PDGF to stimulate cell proliferation and migration (9,11)." provenance.
- _8 value "Ligation of α6β4 in primary human keratinocytes caused tyrosine phosphorylation of Shc, recruitment of Grb2, activation of Ras and stimulation of the MAP kinases Erk and Jnk." provenance.
- _8 value "Ligation of α6β4 in primary human keratinocytes caused tyrosine phosphorylation of Shc, recruitment of Grb2, activation of Ras and stimulation of the MAP kinases Erk and Jnk." provenance.
- _10 value "Ligation of α6β4 in primary human keratinocytes caused tyrosine phosphorylation of Shc, recruitment of Grb2, activation of Ras and stimulation of the MAP kinases Erk and Jnk. In contrast, ligation of the laminin- and collagen-binding integrins α3β1 and α2β1 did not cause these events." provenance.
- _8 value "Ligation of α6β4 in primary human keratinocytes caused tyrosine phosphorylation of Shc, recruitment of Grb2, activation of Ras and stimulation of the MAP kinases Erk and Jnk. In contrast, ligation of the laminin- and collagen-binding integrins α3β1 and α2β1 did not cause these events." provenance.
- _8 value "Ligation of α6β4 in primary human keratinocytes caused tyrosine phosphorylation of Shc, recruitment of Grb2, activation of Ras and stimulation of the MAP kinases Erk and Jnk. In contrast, ligation of the laminin- and collagen-binding integrins α3β1 and α2β1 did not cause these events." provenance.
- _5 value "DKK1 antagonizes Wnt signalling during head formation in mice77. An additional DKK-receptor, Kremen, was shown to inhibit the Wnt signalling pathway by internalization of LRP" provenance.
- _4 value "axin1 and axin2 loss-of-function mutations have also been detected in rare cases of colorectal cancer124,125." provenance.
- _4 value "axin1 and axin2 loss-of-function mutations have also been detected in rare cases of colorectal cancer124,125." provenance.
- _8 value "In the presence of canonical Wnt ligands (FIG. 1b), LRP5-LRP6 is phosphorylated by CK1γ and GSK3β96,97 (and possibly other protein kinases yet to be identified), and Dishevelled is recruited to the plasma membrane, where it interacts with Frizzled receptors and polymerizes with other Dishevelled molecules98,99." provenance.
- _8 value "In the presence of canonical Wnt ligands (FIG. 1b), LRP5-LRP6 is phosphorylated by CK1γ and GSK3β96,97 (and possibly other protein kinases yet to be identified), and Dishevelled is recruited to the plasma membrane, where it interacts with Frizzled receptors and polymerizes with other Dishevelled molecules98,99." provenance.
- _6 value "In the presence of canonical Wnt ligands (FIG. 1b), LRP5-LRP6 is phosphorylated by CK1γ and GSK3β96,97 (and possibly other protein kinases yet to be identified), and Dishevelled is recruited to the plasma membrane, where it interacts with Frizzled receptors and polymerizes with other Dishevelled molecules98,99." provenance.
- _8 value "In the presence of canonical Wnt ligands (FIG. 1b), LRP5-LRP6 is phosphorylated by CK1γ and GSK3β96,97 (and possibly other protein kinases yet to be identified), and Dishevelled is recruited to the plasma membrane, where it interacts with Frizzled receptors and polymerizes with other Dishevelled molecules98,99." provenance.
- _6 value "In the nucleus, β-catenin forms a transcriptionally active complex with LEF and TCF transcription factors30–32 by displacing Grouchos and interacting with other co-activators such as BCL9, Pygopus, CBP (CREB-binding protein) or Hyrax47–51,101–105 (TIMELINE)." provenance.
- _6 value "In the nucleus, β-catenin forms a transcriptionally active complex with LEF and TCF transcription factors30–32 by displacing Grouchos and interacting with other co-activators such as BCL9, Pygopus, CBP (CREB-binding protein) or Hyrax47–51,101–105 (TIMELINE)." provenance.
- _6 value "Moreover, we show that β-catenin and LEF/TCF activate the promoters of BMP4 and N-myc." provenance.
- _5 value "Loss of N-myc function has been shown to result in defective branching morphogenesis in the lung (Moens et al., 1993; Okubo et al., 2005; Sawai et al., 1993; Stanton et al., 1992). Furthermore, N-myc has been recently implicated in the regulation of distal airway progenitor development (Okubo et al., 2005). c-myc, a highly related myc gene, is a well-established down-stream target of Wnt/β-catenin signaling in several tissues including intestinal epithelium (Anna et al., 2003; Cong et al., 2003; Pinto et al., 2003)." provenance.
- _5 value "In SP-C/Dkk1 embryos, however, BMP4 expression is significantly reduced (Fig. 5J). As discussed above, at E12.5, the efficiency of β-catenin excision in many SP-C/rtTA:tetO-cre X β-cateninflox embryos is less than 100% in some embryos resulting in a mosaic pattern of β-catenin expression in the lung airway epithelium. However, this result proves advantageous since we can determine in a precise cell specific manner whether loss of β-catenin leads to a loss of BMP4. As expected, BMP4 and β-catenin are expressed at high levels in distal airway epithelium in wild-type lungs at E12.5 (Figs. 5K– M). Lungs exhibiting mosaic expression of β-catenin also express BMP4 in a mosaic pattern that closely correlates with presence of β-catenin (Figs. 5N–P). Complete loss of β-catenin leads to a complete loss of BMP4 expression (Figs. 5Q–S)." provenance.
- _5 value "In situ hybridization demonstrates that FGFR2 expression is dramatically reduced in lung airway epithelium but not tracheal epithelium of SP-C/rtTA:tetO-cre X h-cateninflox (Figs. 6A and B)." provenance.
- _4 value "Exposure of rats to 80 mg/m3 tobacco smoke significantly induced apoptosis in the lungs. Tobacco smoke resulted in inhibition of NF-κB activity, noted by suppression of inhibitor of κB (IκB) kinase (IKK), accumulation of IκBα, decrease of NF-κB DNA binding activity, and downregulation of NF-κB-dependent anti-apoptotic proteins, including Bcl-2, Bcl-xl, and inhibitors of apoptosis." provenance.
- _4 value "Exposure of rats to 80 mg/m3 tobacco smoke significantly induced apoptosis in the lungs. Tobacco smoke resulted in inhibition of NF-κB activity, noted by suppression of inhibitor of κB (IκB) kinase (IKK), accumulation of IκBα, decrease of NF-κB DNA binding activity, and downregulation of NF-κB-dependent anti-apoptotic proteins, including Bcl-2, Bcl-xl, and inhibitors of apoptosis." provenance.
- _4 value "In order to better understand the underlying mechanisms of tobacco smoke on NF-κB activity, the NF-κB activation pathway was examined. Fig. 4B demonstrates that the levels of the inhibitor of NF-κB (IκB)-α in cytoplasm were significantly elevated in rats exposed to 80 mg/m3 tobacco smoke, whereas the cytoplasmic levels of IκB-α was not changed by tobacco smoke exposure, regardless of concentration." provenance.
- _4 value "Examination of IκB kinases (IKK) revealed that 80 mg/m3 of tobacco smoke suppressed the levels of IKKα and IKKβ phosphorylation (activation). No significant changes were observed for the levels of IKKα and IKKβ activation from rats exposed to 30 mg/m3 tobacco smoke." provenance.
- _4 value "Examination of IκB kinases (IKK) revealed that 80 mg/m3 of tobacco smoke suppressed the levels of IKKα and IKKβ phosphorylation (activation). No significant changes were observed for the levels of IKKα and IKKβ activation from rats exposed to 30 mg/m3 tobacco smoke." provenance.
- _4 value "In line with the NF-κB activity described above, exposure to 80 mg/m3 tobacco smoke significantly down regulated the expression levels of Bcl-2, Bcl-xl, c-IAP1, c-IA2 and XIAP by 49.7%, 67%, 75.9%, 57.1%, and 63.2%, respectively (Fig. 5B)." provenance.
- _4 value "In line with the NF-κB activity described above, exposure to 80 mg/m3 tobacco smoke significantly down regulated the expression levels of Bcl-2, Bcl-xl, c-IAP1, c-IA2 and XIAP by 49.7%, 67%, 75.9%, 57.1%, and 63.2%, respectively (Fig. 5B)." provenance.
- _4 value "In line with the NF-κB activity described above, exposure to 80 mg/m3 tobacco smoke significantly down regulated the expression levels of Bcl-2, Bcl-xl, c-IAP1, c-IA2 and XIAP by 49.7%, 67%, 75.9%, 57.1%, and 63.2%, respectively (Fig. 5B)." provenance.
- _5 value "Apoptosis is executed through the activation of caspases. To further verify the effect of tobacco smoke in the induction of apoptosis, the levels of cleaved caspases 8, 9, and 3 in rat lungs were determined. In agreement with the apoptotic results described above, exposure of rats to 80 mg/m3 tobacco smoke resulted in significantly increased levels of cleaved caspases 8, 9, and 3, indicating the activation of these caspases (Fig. 7B). Compared to FA control animals, the cleaved caspases 8, 9, and 3 were elevated by 98.1%, 113.9%, and 84.7 %, respectively." provenance.
- _9 value "The binding of RB, p107, or p130 has two simultaneous consequences: (1) binding prevents E2F from interacting with transcriptional co-activators (e.g., p300);" provenance.
- _4 value "HBP1 is consistently up regulated in differentiation and under conditions of cell cycle arrest in muscle, adipocyte, erythroid, and other cell types" provenance.
- _6 value "USF1 and USF2 bound the IGF2R promoter in vitro, and both USF1 and USF2, but not c-Myc, were present within the IGF2R promoter-associated chromatin in vivo. Overexpressed USF2, but not USF1, transactivated the IGF2R promoter, and IGF2R mRNA was markedly decreased by expression of a USF-specific dominant negative mutant, identifying IGF2R as a USF2 target." provenance.
- _4 value "In addition, we demonstrate that miR-203 is downregulated during the epithelial commitment of embryonic stem cells, and that overexpression of miR-203 in rapidly proliferating human primary keratinocytes significantly reduces their clonogenic capacity. The results suggest that miR-203, by regulating the ΔNp63 expression level, is a key molecule controlling the p63-dependent proliferative potential of epithelial precursor cells both during keratinocyte differentiation and in epithelial development." provenance.
- _5 value "To further evaluate directly if SOCS-3 is indeed a genuine target of miR-203, we exogenously expressed miR-203 in mouse keratinocytes by infection with adenovirus containing miR-203. Figure 1c (lanes 4–6) shows a slight upregulation of SOCS-3 as compared with keratinocytes infected with adenovirus containing scrambled sequence (lanes 1–3). These data indicate that SOSC-3 is not repressed by miR- 203; conversely its upregulation is presumably independent of miR-203." provenance.
- _7 value "Indeed, we have previously shown that the ubiquitin E3 ligase, Itch, contributes to the reduction in DNp63 protein levels.21" provenance.
- _4 value "However, by none of these means we could detect significant Ang-1 mRNA levels in normal skin, neither in control nor in treated tissue." provenance.
- _5 value "miR-143 and miR-145 expression was also decreased in hearts of Nkx2.5 mutant mouse embryos in a dose-dependent fashion (Fig. 2h)." provenance.
- _5 value "In human embryonic kidney 293 cells, IL-1β induces IκB kinase β (IKKβ) activation, IκBα degradation, NF-κB transactivation, and weak Akt activation." provenance.
- _3 value "However, IL-1β-induced NF-κB activity is attenuated by increased intracellular calcium in response to ionomycin, UTP, or thapsigargin or by overexpression of CaMKKc and/or Akt. Ionomycin and CaMKKc overexpression increases Akt phosphorylation on Thr308 and enzyme activity. Under these conditions or upon overexpression of wild type Akt, IL-1β-induced IKKβ activity is diminished. Furthermore, a dominant negative mutant of Akt abolishes IKKβ inhibition by CaMKKc and ionomycin, suggesting that Akt acts as a mediator of CaMKK signaling to inhibit IL-1β-induced IKK activity at an upstream target site." provenance.
- _3 value "However, IL-1β-induced NF-κB activity is attenuated by increased intracellular calcium in response to ionomycin, UTP, or thapsigargin or by overexpression of CaMKKc and/or Akt. Ionomycin and CaMKKc overexpression increases Akt phosphorylation on Thr308 and enzyme activity. Under these conditions or upon overexpression of wild type Akt, IL-1β-induced IKKβ activity is diminished. Furthermore, a dominant negative mutant of Akt abolishes IKKβ inhibition by CaMKKc and ionomycin, suggesting that Akt acts as a mediator of CaMKK signaling to inhibit IL-1β-induced IKK activity at an upstream target site." provenance.
- _7 value "However, IL-1β-induced NF-κB activity is attenuated by increased intracellular calcium in response to ionomycin, UTP, or thapsigargin or by overexpression of CaMKKc and/or Akt. Ionomycin and CaMKKc overexpression increases Akt phosphorylation on Thr308 and enzyme activity. Under these conditions or upon overexpression of wild type Akt, IL-1β-induced IKKβ activity is diminished. Furthermore, a dominant negative mutant of Akt abolishes IKKβ inhibition by CaMKKc and ionomycin, suggesting that Akt acts as a mediator of CaMKK signaling to inhibit IL-1β-induced IKK activity at an upstream target site." provenance.
- _9 value "However, IL-1β-induced NF-κB activity is attenuated by increased intracellular calcium in response to ionomycin, UTP, or thapsigargin or by overexpression of CaMKKc and/or Akt. Ionomycin and CaMKKc overexpression increases Akt phosphorylation on Thr308 and enzyme activity. Under these conditions or upon overexpression of wild type Akt, IL-1β-induced IKKβ activity is diminished. Furthermore, a dominant negative mutant of Akt abolishes IKKβ inhibition by CaMKKc and ionomycin, suggesting that Akt acts as a mediator of CaMKK signaling to inhibit IL-1β-induced IKK activity at an upstream target site." provenance.
- _5 value "CaMKKc and Akt overexpression decreases IRAK1-mediated NF-κB activity and its association with MyD88 in response to IL-1β stimulation. Furthermore, CaMKKc and Akt overexpression increases IRAK1 phosphorylation at Thr100, and point mutation of this site abrogates the inhibitory effect of Akt on IRAK1-mediated NF-κB activation." provenance.
- _5 value "Probing of immunoblots with antibodies specific for phosphorylated Akt showed that 10 ng/ml of IL-1β slightly increased Akt Thr308 and Ser473 phosphorylation within 60 min (Fig.2). Using histone H2B as an Akt substrate, a slight increase in Akt kinase activity was noted within the same time interval as Akt phosphorylation (Fig. 2)." provenance.
- _6 value "A shows that IL-1β at 10 ng/ml increased IRAK1 activity, which reached a maximum after 10 min and was sustained for at least 90 min." provenance.
- _8 value "Upon stimulation with 10 ng/ml IL-1β for 15 or 30 min, IRAK1 co-immunoprecipitation with MyD88 was enhanced, whereas it was reduced by the overexpression of Akt and CaMKKc (Fig.10,C and D)." provenance.
- _5 value "To study the frequency of JNK induction in human SCC, we probed tissue microarrays of spontaneous human SCC samples (n=52) with antibodies directed against the phosphorylated active forms of JNK. Eighty-one percent of SCCs examined exhibited either strong or moderately strong induction of phosphorylated JNK (pJNK) over normal tissues (Fig. 1A)." provenance.
- _5 value "To investigate whether JNK/AP1 dependency is a general process common to other SCC cell types, we expressed DNc-Jun in spontaneous human SCC cell lines, A431 and SCC25, and found that DNc-Jun significantly inhibited their s.c. tumor growth as well (Fig. 2B–C). Furthermore, retroviral-mediated RNA interference knockdown of MKK7, the upstream activator of JNK, also prevented s.c. tumor growth of A431, SCC25, and primary keratinocytes transformed by Ras and IκBα (Fig. 2B–D)." provenance.
- _5 value "CDK4 is a cyclin-dependent kinase promoting G1 progression previously shown to be posttranscriptionally down-regulated by Ras, a finding whose functional importance has been confirmed because CDK4 can bypass Ras-induced growth arrest (31). CDK4 protein was also restored to near-normal levels by MKK7." provenance.
- _6 value "CDK4 is a cyclin-dependent kinase promoting G1 progression previously shown to be posttranscriptionally down-regulated by Ras, a finding whose functional importance has been confirmed because CDK4 can bypass Ras-induced growth arrest (31). CDK4 protein was also restored to near-normal levels by MKK7." provenance.
- _6 value "Moreover, recent findings showed that epidermal NF-κB blockade relieves constitutive repression of JNK activity by the NF-κB RelA subunit and that TNFR1 is required both for the JNK induction as well as the epidermal hyperplasia that occurs in this setting (16,17)." provenance.
- _7 value "inhibition of fibroblast proliferation was mediated exclusively by activation of Epac-1. PGE2 and Epac-1 inhibited cell proliferation through activation of the small GTPase Rap1, since decreasing Rap1 activity by transfection with Rap1GAP or the dominant-negative Rap1N17 prevented, and transfection with the constitutively active Rap1V12 mimicked, the anti-proliferative effects of PGE2" provenance.
- _5 value "inhibition of fibroblast proliferation was mediated exclusively by activation of Epac-1. PGE2 and Epac-1 inhibited cell proliferation through activation of the small GTPase Rap1, since decreasing Rap1 activity by transfection with Rap1GAP or the dominant-negative Rap1N17 prevented, and transfection with the constitutively active Rap1V12 mimicked, the anti-proliferative effects of PGE2" provenance.
- _5 value "Work in our laboratory (13) and others (14) has shown that the inhibitory actions of PGE2 in lung fibroblasts are a result of increases in cAMP, mediated through the Gas-coupled EP2 receptor;" provenance.
- _5 value "Work in our laboratory (13) and others (14) has shown that the inhibitory actions of PGE2 in lung fibroblasts are a result of increases in cAMP, mediated through the Gas-coupled EP2 receptor;" provenance.
- _3 value "Work in our laboratory (13) and others (14) has shown that the inhibitory actions of PGE2 in lung fibroblasts are a result of increases in cAMP, mediated through the Gas-coupled EP2 receptor;" provenance.
- _5 value "We found that both PGE2 and the Epac agonist stimulated Rap1 activity, as measured by the RalGDS pulldown of active GTP-loaded Rap1, whereas the PKA agonist actually had an inhibitory effect on Rap1 activity (Figure 4A)." provenance.
- _5 value "We found that both PGE2 and the Epac agonist stimulated Rap1 activity, as measured by the RalGDS pulldown of active GTP-loaded Rap1, whereas the PKA agonist actually had an inhibitory effect on Rap1 activity (Figure 4A)." provenance.
- _5 value "Inhibition with the specific PKC-δ inhibitor rottlerin resulted in decreased collagen expression (Figure 5C)" provenance.
- _4 value "In keeping with the agonist data, cells expressing PKACα exhibited a reduction in collagen expression, but not in proliferation (Figure 2A)" provenance.
- _5 value "Rin1 depletion from A549 cells resulted in a decrease in cell proliferation that was correlated to a decrease in epidermal growth factor receptor (EGFR) signaling. Expression of wild type Rin1 but not the Rab5 guanine nucleotide exchange factor-deficient Rin1 (Rin1Δ) complemented the Rin1 depletion effects, and overexpression of Rin1Δ had a dominant negative effect on cell proliferation." provenance.
- _7 value "To confirm that EGFR internalization was critical for potentiating EGFR signaling, a GFP-tagged dominant negative dynamin (dn-dynamin) K44A expression construct was transiently transfected into A549 cells, and the impact of its expression on EGF-stimulated signaling was determined (Fig. 7A). The expression of dn-dynamin (Fig. 7B) resulted in a ~2-fold decrease in ERK1/2 activation in response to EGF stimulation (Fig. 7, A and C); this observation supports the conclusion that internalization of EGFR is critical for proper signaling in A549 cells." provenance.
- _6 value "To confirm that EGFR internalization was critical for potentiating EGFR signaling, a GFP-tagged dominant negative dynamin (dn-dynamin) K44A expression construct was transiently transfected into A549 cells, and the impact of its expression on EGF-stimulated signaling was determined (Fig. 7A). The expression of dn-dynamin (Fig. 7B) resulted in a ~2-fold decrease in ERK1/2 activation in response to EGF stimulation (Fig. 7, A and C); this observation supports the conclusion that internalization of EGFR is critical for proper signaling in A549 cells." provenance.
- _7 value "To test the role of Rab5 in these processes, A549 cells were transfected with a GFP-tagged dominant negative Rab5 S34N (GFP-dnRab5) expression construct (Fig. 7A). Similar to the results with Rin1 depletion, expression of GFP-dnRab5 resulted in a ~2-fold decrease in pERK levels when compared with control cells expressing GFP alone." provenance.
- _7 value "Finally, to confirm that dnRab5 and dn-dynamin expression impacted cell proliferation in a manner similar to Rin1 depletion, A549 cells transiently transfected with expression constructs encoding GFP-dnRab5, GFP-dn-dynamin, or GFP alone were tested for their ability to form colonies (Fig. 8). Cells transfected with GFP-dnRab5 or GFP-dn-dynamin expression constructs showed decreased cell proliferation, supporting the conclusion that proper EGFR internalization and Rab5-mediated endosomal trafficking of EGFR are critical for potentiating proliferative signaling in A549 cells." provenance.
- _4 value "Gene expression from 186 human lung tumors with associated clinical information were surveyed for statistically significant variations in RIN1 mRNA levels (34). Of three Rin1 probe sets on the Affymetrix U95 array, one probe set (1777_at) was significantly up-regulated in adenocarcinoma, bronchioalveolar carcinoma, metastatic adenocarcinoma, and carcinoid and squamous cell carcinoma compared with normal lung (Fig. 9). The other two probe sets demonstrated statistically significant up-regulation in both squamous cell carcinoma and metastatic adenocarcinoma of the lung." provenance.
- _4 value "In human pancreatic islets, specific insulin biosynthesis, i.e. after normalization to total protein biosynthesis, increased by 2-fold (P < 0.01) upon stimulation with glucose and by 2.3-fold (P < 0.01) upon stimulation with insulin (Fig.1)" provenance.
- _9 value "Triggering of the IL-1R or TLR causes the adaptor protein MyD88 to be recruited to the receptor complex, which in turn promotes association with the IL-1R-associated kinases IRAK4 and IRAK1. During the formation of this complex, IRAK4 is activated, leading to the hyperphosphorylation of IRAK-1, which then induces the interaction of TRAF6 with the complex." provenance.
- _4 value "We have observed previously that adhesion of normal HB2 cells to collagen I is accompanied by a collagen-induced phosphorylation of DDR1.9 The present experiments show that adhesion to collagen IV also causes a phosphorylation of DDR1 in mammary epithelial cells (Fig.1b)." provenance.
- _6 value "To explore the mechanism(s) involved in the Wnt-5a-dependent effects on collagen-induced phosphorylation of DDR1 in mammary epithelial cells and on adhesion of such cells to collagen,9 we first tested the impact of pertussis and cholera toxins on the collagen-induced phosphorylation of DDR1 in normal HB2 cells. We found that the phosphorylation was almost abolished by pertussis toxin (Fig. 2a,b), but was not affected by cholera toxin (Fig. 2c)." provenance.
- _5 value "Furthermore, we tested the effects of pertussis toxin on Wnt-5a-deficient HB2 (Fig. 4a) and MCF-7 mammary tumor (Fig. 4b) cells. As expected, both of these Wnt-5a-deficient cell lines exhibited significantly less adhesion that reached a maximum (50–60% of the plated cells) after 90–120 min (Fig. 4), which is nearly half of the adhesive capacity of Wnt-5a-expressing HB2 cells (Fig. 3)." provenance.
- _5 value "To further ascertain whether such a link exists between Wnt-5a signaling, collagen-induced DDR1 activation, and the adhesiveness of HB2 cells, we tested the effects of PP1, a specific inhibitor of Src family tyrosine kinases. We found that PP1 abolished the collagen-induced phosphorylation of DDR1 (Fig. 6a), and that it also decreased adhesion of normal HB2 cells by about 50% (Fig. 6b)." provenance.
- _6 value "Furthermore, we noted that collagen-stimulated DDR1 interacted with the p85 subunit of PI3K (Fig. 7b), and we also observed that adherence of HB2 cells to collagen caused tyrosine phosphorylation of the p85 of PI3K (Fig. 7c), a phenomenon associated with activation of this enzyme. Neither of these events was observed in cells pretreated with pertussis toxin (Fig. 7a,b,c)." provenance.