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121.
Inhibition of integrin-mediated crosstalk with epidermal growth factor receptor/Erk or Src signaling pathways in autophagic prostate epithelial cells induces caspase-independent death
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In vivo in the prostate gland, basal epithelial cells adhere to laminin 5 (LM5) via alpha3beta1 and alpha6beta4 integrins. When placed in culture primary prostate basal epithelial cells secrete and adhere to their own LM5-rich matrix. Adhesion to LM5 is required for cell survival that is dependent on integrin-mediated, ligand-independent activation of the epidermal growth factor receptor (EGFR) and the cytoplasmic tyrosine kinase Src, but not PI-3K. Integrin-mediated adhesion via alpha3beta1, but not alpha6beta4 integrin, supports cell survival through EGFR by signaling downstream to Erk. PC3 cells, which do not activate EGFR or Erk on LM5-rich matrices, are not dependent on this pathway for survival. PC3 cells are dependent on PI-3K for survival and undergo caspase-dependent death when PI-3K is inhibited. The death induced by inhibition of EGFR or Src in normal primary prostate cells is not mediated through or dependent on caspase activation, but depends on the induction of reactive oxygen species. In addition the presence of an autophagic pathway, maintained by adhesion to matrix through alpha3beta1 and alpha6beta4, prevents the induction of caspases when EGFR or Src is inhibited. Suppression of autophagy is sufficient to induce caspase activation and apoptosis in LM5-adherent primary prostate epithelial cells. 相似文献
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Bizzarri AR Brunori E Bonanni B Cannistraro S 《Journal of molecular recognition : JMR》2007,20(2):122-131
We coupled protein-protein docking procedure with molecular dynamics (MD) simulation to investigate the electron transfer (ET) complex Azurin-Cytochrome c551 whose transient character makes difficult a direct experimental investigation. The ensemble of complexes generated by the docking algorithm are filtered according to both the distance between the metal ions in the redox centres of the two proteins and to the involvement of suitable residues at the interface. The resulting best complex (BC) is characterized by a distance of 1.59 nm and involves Val23 and Ile59 of Cytochrome c551. The ET properties have been evaluated in the framework of the Pathways model and compared with experimental data. A 60 ns long MD simulation, carried on at full hydration, evidenced that the two protein molecules retain their mutual spatial positions upon forming the complex. An analysis of the ET properties of the complex, monitored at regular time intervals, has revealed that several different ET paths are possible, with the occasional intervening of water molecules. Furthermore, the temporal evolution of the geometric distance between the two redox centres is characterized by very fast fluctuations around an average value of 1.6 nm, with periodic jumps at 2 nm with a frequency of about 70 MHz. Such a behaviour is discussed in connection with a nonlinear dynamics of protein systems and its possible implications in the ET process are explored. 相似文献
124.
Moese S Selbach M Brinkmann V Karlas A Haimovich B Backert S Meyer TF 《Cellular microbiology》2007,9(5):1148-1161
Helicobacter pylori colonizes the human stomach, contributing to or causing several diseases. Translocation of the CagA bacterial protein into gastric epithelial cells has been linked to an increased risk of peptic ulcer disease and gastric carcinoma. Upon translocation, CagA is tyrosine phosphorylated by Src family kinases (SFKs), which themselves become inactivated via a negative feedback loop. Here, we show that tyrosine-phosphorylated CagA disrupts adhesion of AGS cells to the extracellular matrix. Owing to the inactivation of c-Src via CagA interaction, vinculin is dephosphorylated at tyrosine residues, 100 and 1065, by corresponding phosphatases. Vinculin dephosphorylation disturbs the interaction and recruitment of the actin-related protein 2/3 (Arp2/3) complex by p34Arc, resulting in a reduction of focal adhesion complexes. These defects can be mimicked by downregulating vinculin using RNA interference in non-infected cells. Tyrosine dephosphorylation of vinculin results in severe cellular deficiencies in cell-matrix adhesion, cell spreading and wound repair. We hypothesize that CagA-mediated inactivation of vinculin is a key step in the mechanism by which H. pylori induces damage to the gastric epithelium and represents an important step in disease development. 相似文献
125.
Virginie?Barraud-Lange Nathalie?Naud-Barriant Line?Saffar Liliane?Gattegno Beatrice?Ducot Anne-Sophie?Drillet Morgane?Bomsel Jean-Philippe?WolfEmail author Ahmed?Ziyyat 《BMC developmental biology》2007,7(1):102
Background
Based on inhibition tests, the alpha6beta1 integrin was suggested to be a sperm receptor, but further experiments using gene deletion techniques have shown that neither oocyte alpha6, nor beta1 integrin subunits were essential for mouse fertilization. 相似文献126.
Monomeric and Dimeric 9‐O Anthraquinone and Phenanthryl Derivatives of Cinchona Alkaloids as Chiral Solvating Agents for the NMR Enantiodiscrimination of Chiral Hemiesters
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Gloria Uccello Barretta Alessandro Mandoli Federica Balzano Federica Aiello Beatrice De Nicola Alessandro Del Grande 《Chirality》2015,27(10):693-699
Mono‐ and bis‐alkaloid chiral auxiliaries with anthraquinone or phenanthryl cores were probed as chiral solvating agents (CSAs) for the enantiodiscrimination of chiral cyclic hemiesters. The dimeric anthraquinone derivative and the monomeric phenanthryl one showed remarkable efficiency in the nuclear magnetic resonance (NMR) differentiation of enantiomeric mixtures of hemiesters. An anthraquinone analogous with a single alkaloid unit was remarkably less effective. The conformational prevalence of the chiral auxiliaries were ascertained by NMR. Chirality 27:693–699, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
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Glucagon signalling in the dorsal vagal complex is sufficient and necessary for high‐protein feeding to regulate glucose homeostasis in vivo
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Mary P LaPierre Mona A Abraham Jessica TY Yue Beatrice M Filippi Tony KT Lam 《EMBO reports》2015,16(10):1299-1307
High‐protein feeding acutely lowers postprandial glucose concentration compared to low‐protein feeding, despite a dichotomous rise of circulating glucagon levels. The physiological role of this glucagon rise has been largely overlooked. We here first report that glucagon signalling in the dorsal vagal complex (DVC) of the brain is sufficient to lower glucose production by activating a Gcgr–PKA–ERK–KATP channel signalling cascade in the DVC of rats in vivo. We further demonstrate that direct blockade of DVC Gcgr signalling negates the acute ability of high‐ vs. low‐protein feeding to reduce plasma glucose concentration, indicating that the elevated circulating glucagon during high‐protein feeding acts in the brain to lower plasma glucose levels. These data revise the physiological role of glucagon and argue that brain glucagon signalling contributes to glucose homeostasis during dietary protein intake. 相似文献
130.
Nahla V Bassil Thomas M Davis Hailong Zhang Stephen Ficklin Mike Mittmann Teresa Webster Lise Mahoney David Wood Elisabeth S Alperin Umesh R Rosyara Herma Koehorst-vanc Putten Amparo Monfort Daniel J Sargent Iraida Amaya Beatrice Denoyes Luca Bianco Thijs van Dijk Ali Pirani Amy Iezzoni Dorrie Main Cameron Peace Yilong Yang Vance Whitaker Sujeet Verma Laurent Bellon Fiona Brew Raul Herrera Eric van de Weg 《BMC genomics》2015,16(1)