Matches in Nanopublications for { ?s <http://www.w3.org/ns/prov#value> ?o ?g. }
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- _4 value "Primary brown adipocytes pretreated with this compound before insulin stimulation showed a marked increase in IRS-1/2 serine phosphorylation with a concomitant decrease in tyrosine phosphorylation of these molecules and a partial inhibition of IRS-1- and IRS-2-associated PI 3-kinase activity [53]." provenance.
- _7 value "The metabolic consequence of PKCz inhibition is a blockade of insulin-induced glucose uptake." provenance.
- _5 value "PD098059 blocks the activity of MEK and not that of MAPK. In addition, PD098059 did not inhibit a number of other kinase activities both in vitro and in cultured cells. These include Raf kinase, PKC, cyclic AMP-dependent kinase, vsrc kinase, PDGF receptor tyrosine kinase and PI 3-kinase" provenance.
- _4 value "PD098059 blocks the activity of MEK and not that of MAPK. In addition, PD098059 did not inhibit a number of other kinase activities both in vitro and in cultured cells. These include Raf kinase, PKC, cyclic AMP-dependent kinase, vsrc kinase, PDGF receptor tyrosine kinase and PI 3-kinase" provenance.
- _7 value "pretreatment of rat fetal brown adipocytes in primary culture with TNFα inhibited insulin-induced expression of several adipogenic differentiation mRNAs markers such as FAS and G3PD" provenance.
- _4 value "IRS-1 has recently been described as an essential signaling molecule, acting through PI 3-kinase, in the differentiation of brown adipocytes in vitro based on protocols developed in mouse fibroblasts [67] and in brown fat preadipocytes [56]." provenance.
- _8 value "IRS-2-deficient brown adipocytes insulin-induced effect on GLUT4 translocation to the plasma membrane was impaired [76]." provenance.
- _4 value "increased GLUT4 expression has been reported in adipocytes treated with TZD [82]." provenance.
- _4 value "IRS-2 protein expression increased after TZD treatment in murine 3T3-L1 and human adipocytes [85]." provenance.
- _4 value "Previous work reported by Angel et al. [94] demonstrated that GLUT4 mRNA and protein levels are decreased in WAT and BAT of Type 2 diabetic rats." provenance.
- _4 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.
- _5 value "The epidermis develops depending on the transcription factor p63, a member of the p53 family of transcription factors." provenance.
- _5 value "Here we report that microRNA (miR)-203 is induced in vitro in primary keratinocytes in parallel with differentiation. We found that miR-203 specifically targets human and mouse p63 3'-UTRs and not SOCS-3, despite bioinformatics alignment between miR-203 and SOCS-3 3'-UTR." provenance.
- _4 value "As shown in Figure 1a and b, miR-203 was rapidly upregulated (about 12-fold in mouse keratinocytes upon 24 h calcium treatment) when cells where induced by calcium to differentiate in vitro. Concurrently, with miR-203 upregulation, we observed DNp63 downregulation in differentiating cells (Figure 1a and b)." provenance.
- _4 value "Embryonic stem cells can recapitulate in vitro the main steps of embryonic epidermal differentiation upon exogenous addition of bone morphogenic protein (BMP)-4." provenance.
- _4 value "Besides the epidermis and other stratified squamous epithelia, ΔNp63 is commonly overexpressed in up to 80% of primary head and neck squamous cell carcinomas (HNSCCs).29" provenance.
- _4 value "As shown in Figure 6a, ΔNp63 expression was already decreased in JHU-012 cells 12 h after UVC treatment. Simultaneously, with DNp63 downregulation, miR-203 was significantly upregulated as evaluated by real-time PCR (Figure 6b)." provenance.
- _5 value "targeting VEGFR-2 plus the platelet- derived growth factor receptor (PDGFR)-β system (PDGFR- β) signaling (by SU6668) rapidly forced 40% of tumor blood vessels into regression, rendering these tumors hypoxic as shown by phosphorescence quenching." provenance.
- _4 value "Whereas expression of the VEGF and FGF systems remained largely unchanged, expression of PDGFR-β and Tie2 were nearly doubled and expression of Ang-1 was increased by nine fold in SU5416- treated tumors (Fig. 3A-C)." 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 "lentiviral-mediated introduction of miR-145 into ligated mouse carotid arteries in vivo increased expression of markers of VSMC differentiation (e.g., Calponin and Sm-α-actin), as well as Myocd, compared to control-infected injured carotid arteries (Supplementary Fig. 7)." provenance.
- _6 value "Nkx2.5 could also independently activate this enhancer (miR-143/145 enhancer), and the combination of SRF, Myocd, and Nkx2.5, which also interacts with SRF26, had additive effects on luciferase activity. Mutation of each binding site progressively decreased luciferase activity (Fig. 2f)." provenance.
- _6 value "Nkx2.5 could also independently activate this enhancer (miR-143/145 enhancer), and the combination of SRF, Myocd, and Nkx2.5, which also interacts with SRF26, had additive effects on luciferase activity. Mutation of each binding site progressively decreased luciferase activity (Fig. 2f)." provenance.
- _8 value "Nkx2.5 could also independently activate this enhancer (miR-143/145 enhancer), and the combination of SRF, Myocd, and Nkx2.5, which also interacts with SRF26, had additive effects on luciferase activity. Mutation of each binding site progressively decreased luciferase activity (Fig. 2f)." provenance.
- _5 value "introduction of miR-145, but not miR-143, with the luciferase vector in Cos cells resulted in relief of the repression and an ~150-fold increase in luciferase activity compared to the CMV-luciferase- Myocd 3' UTR-luciferase vector alone (Fig. 4d)." provenance.
- _7 value "SRF weakly activated the miR-143/145 enhancer upstream of a luciferase reporter, but co-transfection of Myocd synergistically and robustly activated luciferase activity in Cos cells (Fig. 2f)." provenance.
- _6 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.
- _6 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.
- _6 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 "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 "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.
- _6 value "In cells transfected with negative mutants of IKKα, IKKβ, and NIK, IL-1β-induced κB luciferase activity were inhibited by 32 ± 7%, 70 ± 11%, and 33 ± 8%, respectively (Fig. 1D). Compared with the distinct selectivity for IL-1β action, IKKα and IKKβ mutants reduced the NIK-induced κB response to a similar extent (Fig. 1D)." 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.
- _9 value "IL-1β-induced IRAK1 activity was inhibited by treatment with ionomycin or overexpression of CaMKKc and Akt." provenance.
- _7 value "IL-1β-induced IRAK1 activity was inhibited by treatment with ionomycin or overexpression of CaMKKc and Akt." provenance.
- _5 value "To address this, we first studied the effect of a JNK-specific inhibitor, SP600125 (30), which has been shown to inhibit JNK function and epidermal hyperplasia in epidermis expressing IκBα or deficient in relA (16)." provenance.
- _5 value "Ras-driven epidermal neoplasias generated on the surface of immunodeficient SCID mice were treated topically with DMSO vehicle or SP600125 daily for 5 weeks. DMSO and untreated control tissues displayed typical findings of neoplasia, including invasion and disruption of the BMZ, as visualized by type VII collagen staining (Fig. 2A). In contrast, tissues treated with SP600125 lacked invasive neoplasia and retained sharp delineation of the BMZ, with a humanspecific desmoglein-3 antibody confirming the human origin of these tissues (Fig. 2A)." provenance.
- _6 value "Of interest, although Ras by itself activates AP1, coexpression of Ras with MKK7 induces significantly higher levels of AP1 activity in primary human keratinocytes than either one alone (Supplementary Fig. S5), indicating that Ras and MKK7 act in synergy to induce downstream signaling." provenance.
- _4 value "In support of this, TNFR1 has recently been implicated in murine epidermal tumorigenesis. Genetic deletion of Tnfr1 diminished occurrence of neoplasia in mice induced by both NF-κB blockade and chemical carcinogenesis (33,34)." 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.
- _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.
- _3 value "the Epac agonist elicited a dose-dependent decrease in proliferation but had no effect on collagen expression (Figure 1D)" provenance.
- _5 value "cells expressing PKACα exhibited a reduction in collagen expression, but not in proliferation (Figure 2A)" 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 "Inhibition with the specific PKC-δ inhibitor rottlerin resulted in decreased collagen expression (Figure 5C)" provenance.
- _3 value "The PKA agonist dose-dependently inhibited collagen expression but had no effect on proliferation (Figure 1C)" provenance.
- _5 value "In keeping with the agonist data, cells expressing PKACα exhibited a reduction in collagen expression, but not in proliferation (Figure 2A)" provenance.
- _7 value "Rin1 depletion stabilized the cell surface levels of EGFR, suggesting that internalization was necessary for robust signaling in A549 cells. In support of this conclusion, introduction of either dominant negative Rab5 or dominant negative dynamin decreased A549 proliferation and EGFR signaling." provenance.
- _8 value "However, Rin1Δ expression did not complement Rin1 knockdown defects but instead caused further inhibition of cell proliferation (Fig. 4E). These results suggest that a functional Vps9 domain is critical for Rin1 activity in EGFR-mediated cell proliferation. To verify that the Rin1 Vps9 domain was important for A549 cell proliferation, Rin1Δ or wild type Rin1 expression constructs were transfected into A549 cells and assayed for colony formation (Fig. 5, A and B). Only Rin1Δ expression but not wild type Rin1 expression resulted in decreased cell proliferation. These results indicated that Rin1 lacking a functional Vps9 domain acted as a dominant negative, suggesting that the trafficking roles of Rin1 were mediating EGFR proliferative signaling in A549 cells." 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.
- _5 value "in control RIN β-cells, specific insulin biosynthesis increased by 1.9-fold (P < 0.001) upon stimulation with glucose and by 2.0-fold (P < 0.001) upon stimulation with insulin (Fig.2). Insulin biosynthesis in RIN β-cells exposed to glucosamine was reduced by 40% upon glucose stimulation (P < 0.001) and by 45% upon insulin stimulation (P < 0.01) as compared with untreated control β-cells." provenance.
- _7 value "we combined the stimulation with glucose or insulin with the cotreatment with inhibitors of the insulin receptor tyrosine kinase [hydroxy-2-naphthalenylmethylphosphonic acid trisacetoxymethyl ester (HNMPA)], PI 3-kinase (wortmannin and LY294002), and mTOR (rapamycin). As shown in Figs. 1 and 2, HNMPA, wortmannin, LY294002, and rapamycin inhibited both glucose- and insulin-stimulated insulin biosynthesis in both human pancreatic islets and RIN β-cells." provenance.
- _6 value "As shown in Fig. 4, insulin-stimulated Tyr608 and Tyr628 phosphorylation of IRS-1 was decreased by 30 and 46%, respectively, in RIN β-cells exposed to glucosamine as compared with control RIN β-cells." provenance.
- _5 value "Inhibition of hexosamine biosynthesis by the GFAT inhibitor azaserine reversed the stimulatory effects of glucose on JNK, c-Jun, and ERK1/2 activation (Fig. 9, A–C) as well as IRS-1 phosphorylation at Ser307 and Ser612 (Fig. 10, A and B)." provenance.
- _6 value "Inhibition of hexosamine biosynthesis by the GFAT inhibitor azaserine reversed the stimulatory effects of glucose on JNK, c-Jun, and ERK1/2 activation (Fig. 9, A–C) as well as IRS-1 phosphorylation at Ser307 and Ser612 (Fig. 10, A and B)." provenance.
- _5 value "Exposure of RIN β-cells to glucosamine increased phosphorylation of both IRS-1 Ser307 and IRS-1 Ser612, which was reversed by treatment with either a cell-permeable JNK inhibitor or PD98059, a reversible MAPK kinase (MEK)1 inhibitor, the enzyme that directly activates ERK1/2, respectively (Fig. 10, A and B)" 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.