u-0126 has been researched along with jasplakinolide* in 3 studies
3 other study(ies) available for u-0126 and jasplakinolide
Article | Year |
---|---|
MEK modulates force-fluctuation-induced relengthening of canine tracheal smooth muscle.
Tidal breathing, and especially deep breathing, is known to antagonise bronchoconstriction caused by airway smooth muscle (ASM) contraction; however, this bronchoprotective effect of breathing is impaired in asthma. Force fluctuations applied to contracted ASM in vitro cause it to relengthen, force-fluctuation-induced relengthening (FFIR). Given that breathing generates similar force fluctuations in ASM, FFIR represents a likely mechanism by which breathing antagonises bronchoconstriction. Thus it is of considerable interest to understand what modulates FFIR, and how ASM might be manipulated to exploit this phenomenon. It was demonstrated previously that p38 mitogen-activated protein kinase (MAPK) signalling regulates FFIR in ASM strips. Here, it was hypothesised that the MAPK kinase (MEK) signalling pathway also modulates FFIR. In order to test this hypothesis, changes in FFIR were measured in ASM treated with the MEK inhibitor, U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene). Increasing concentrations of U0126 caused greater FFIR. U0126 reduced extracellular signal-regulated kinase 1/2 phosphorylation without affecting isotonic shortening or 20-kDa myosin light chain and p38 MAPK phosphorylation. However, increasing concentrations of U0126 progressively blunted phosphorylation of high-molecular-weight caldesmon (h-caldesmon), a downstream target of MEK. Thus changes in FFIR exhibited significant negative correlation with h-caldesmon phosphorylation. The present data demonstrate that FFIR is regulated through MEK signalling, and suggest that the role of MEK is mediated, in part, through caldesmon. Topics: Animals; Butadienes; Depsipeptides; Dogs; Enzyme Inhibitors; Mitogen-Activated Protein Kinase Kinases; Muscle Contraction; Muscle, Smooth; Nitriles; Phosphorylation; Signal Transduction; Tidal Volume; Tissue Distribution; Trachea | 2010 |
Insulin-like growth factor I controls adhesion strength mediated by alpha5beta1 integrins in motile carcinoma cells.
One of the intriguing questions regarding cell motility concerns the mechanism that makes stationary cells move. Here, we provide the first physical evidence that the onset of breast cancer cell motility in response to insulin-like growth factor I (IGF-I) correlates with lowering of adhesion strength from 2.52 +/- 0.20 to 1.52 +/- 0.13 microdynes/microm2 in cells attached to fibronectin via alpha5beta1 integrin. The adhesion strength depends on the dose of IGF-I and time of IGF-I treatment. Weakening of cell-matrix adhesion is blocked significantly (p < 0.01) by the catalytically inactive IGF-I receptor (IGF-IR) and the phosphoinositide 3-kinase (PI-3 kinase) inhibitor LY-294002, but it is unaffected by mitogen-activated protein kinase kinase inhibitor UO-126 and Src kinase inhibitor PP2. Sustained blockade of Rho-associated kinase (ROCK) with Y-27632 down-regulates adhesion strength in stationary, but not in IGF-I-treated, cells. Jasplakinolide, a drug that prevents actin filament disassembly, counteracts the effect of IGF-I on integrin-mediated cell adhesion. In the absence of growth factor signaling, ROCK supports a strong adhesion via alpha5beta1 integrin, whereas activation of the IGF-IR kinase reduces cell-matrix adhesion through a PI-3K-dependent, but ROCK-independent, mechanism. We propose that disassembly of the actin filaments via PI-3 kinase pathway contributes to weakening of adhesion strength and induction of cell movement. Understanding how cell adhesion and migration are coordinated has an important application in cancer research, developmental biology, and tissue bioengineering. Topics: Actins; Amides; Blotting, Western; Breast Neoplasms; Butadienes; Carcinoma; Catalysis; Cell Adhesion; Cell Line, Tumor; Cell Movement; Chromones; CSK Tyrosine-Protein Kinase; Culture Media, Serum-Free; Depsipeptides; Down-Regulation; Fibronectins; Flow Cytometry; Humans; Immunoprecipitation; Insulin-Like Growth Factor I; Integrin alpha5beta1; Intracellular Signaling Peptides and Proteins; MAP Kinase Signaling System; Microscopy, Phase-Contrast; Models, Biological; Morpholines; Nitriles; Phosphatidylinositol 3-Kinases; Phosphorylation; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Protein-Tyrosine Kinases; Pyridines; Pyrimidines; rho GTP-Binding Proteins; rho-Associated Kinases; Signal Transduction; src-Family Kinases; Time Factors | 2005 |
Involvement of the mitogen-activated protein kinase SIMK in regulation of root hair tip growth.
Mitogen-activated protein kinases (MAPKs) are involved in stress signaling to the actin cytoskeleton in yeast and animals. We have analyzed the function of the stress-activated alfalfa MAP kinase SIMK in root hairs. In epidermal cells, SIMK is predominantly nuclear. During root hair formation, SIMK was activated and redistributed from the nucleus into growing tips of root hairs possessing dense F-actin meshworks. Actin depolymerization by latrunculin B resulted in SIMK relocation to the nucleus. Conversely, upon actin stabilization with jasplakinolide, SIMK co-localized with thick actin cables in the cytoplasm. Importantly, latrunculin B and jasplakinolide were both found to activate SIMK in a root-derived cell culture. Loss of tip-focused SIMK and actin was induced by the MAPK kinase inhibitor UO 126 and resulted in aberrant root hairs. UO 126 inhibited targeted vesicle trafficking and polarized growth of root hairs. In contrast, overexpression of gain-of-function SIMK induced rapid tip growth of root hairs and could bypass growth inhibition by UO 126. These data indicate that SIMK plays a crucial role in root hair tip growth. Topics: Actin Cytoskeleton; Actins; Active Transport, Cell Nucleus; Bridged Bicyclo Compounds, Heterocyclic; Butadienes; Cell Nucleus; Cell Polarity; Cell Surface Extensions; Cytoplasm; Depsipeptides; Enzyme Activation; MAP Kinase Signaling System; Medicago sativa; Microscopy, Video; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Nicotiana; Nitriles; Peptides, Cyclic; Plant Proteins; Plant Roots; Recombinant Fusion Proteins; Thiazoles; Thiazolidines | 2002 |