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000032540 084__ $$2WoS$$aBiochemistry & Molecular Biology
000032540 1001_ $$0P:(DE-HGF)0$$avom Dahl, S.$$b0
000032540 245__ $$aInvolvement of integrins in osmosensing and signaling towards autophagic proteolysis in rat liver
000032540 260__ $$aBethesda, Md.$$bSoc.$$c2003
000032540 300__ $$a27088 - 27095
000032540 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
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000032540 440_0 $$03091$$aJournal of Biological Chemistry$$v278$$x0021-9258
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000032540 520__ $$aInhibition of autophagic proteolysis by hypoosmotic or amino acid-induced hepatocyte swelling requires osmosignaling toward p38MAPK; however, the upstream osmosensing and signaling events are unknown. These were studied in the intact perfused rat liver with a preserved in situ environment of hepatocytes. It was found that hypoosmotic hepatocyte swelling led to an activation of Src (but not FAK), Erks, and p38MAPK, which was prevented by the integrin inhibitory hexapeptide GRGDSP, but not its inactive analogue GRGESP. Src inhibition by PP-2 prevented hypoosmotic MAP kinase activation, indicating that the integrin/Src system is located upstream in the osmosignaling toward p38MAPK and Erks. Inhibition of the integrin/Src system by the RGD motif-containing peptide or PP-2 also prevented the inhibition of proteolysis and the decrease in autophagic vacuole volume, which is otherwise observed in response to hypoosmotic or glutamine/glycine-induced hepatocyte swelling. These inhibitors, however, did not affect swelling-independent proteolysis inhibition by phenylalanine. In line with a role of p38MAPK in triggering the volume regulatory decrease (RVD), PP-2 and the RGD peptide blunted RVD in response to hypoosmotic cell swelling. The data identify integrins and Src as upstream events in the osmosignaling toward MAP kinases, proteolysis, and RVD. They further point to a role of integrins as osmo- and mechanosensors in the intact liver, which may provide a link between cell volume and cell function.
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000032540 650_2 $$2MeSH$$aAnimals
000032540 650_2 $$2MeSH$$aAutophagy
000032540 650_2 $$2MeSH$$aCell Size: drug effects
000032540 650_2 $$2MeSH$$aCell Size: physiology
000032540 650_2 $$2MeSH$$aCells, Cultured
000032540 650_2 $$2MeSH$$aHepatocytes: cytology
000032540 650_2 $$2MeSH$$aHepatocytes: drug effects
000032540 650_2 $$2MeSH$$aHepatocytes: physiology
000032540 650_2 $$2MeSH$$aIntegrins: antagonists & inhibitors
000032540 650_2 $$2MeSH$$aIntegrins: physiology
000032540 650_2 $$2MeSH$$aLiver: drug effects
000032540 650_2 $$2MeSH$$aLiver: physiology
000032540 650_2 $$2MeSH$$aLiver: ultrastructure
000032540 650_2 $$2MeSH$$aMAP Kinase Signaling System
000032540 650_2 $$2MeSH$$aMale
000032540 650_2 $$2MeSH$$aMitogen-Activated Protein Kinases: metabolism
000032540 650_2 $$2MeSH$$aModels, Biological
000032540 650_2 $$2MeSH$$aOligopeptides: pharmacology
000032540 650_2 $$2MeSH$$aPerfusion
000032540 650_2 $$2MeSH$$aRats
000032540 650_2 $$2MeSH$$aRats, Wistar
000032540 650_2 $$2MeSH$$aSignal Transduction
000032540 650_2 $$2MeSH$$aWater-Electrolyte Balance: physiology
000032540 650_2 $$2MeSH$$ap38 Mitogen-Activated Protein Kinases
000032540 650_2 $$2MeSH$$asrc-Family Kinases: antagonists & inhibitors
000032540 650_2 $$2MeSH$$asrc-Family Kinases: metabolism
000032540 650_7 $$00$$2NLM Chemicals$$aIntegrins
000032540 650_7 $$00$$2NLM Chemicals$$aOligopeptides
000032540 650_7 $$091037-75-1$$2NLM Chemicals$$aglycyl-arginyl-glycyl-aspartyl-seryl-proline
000032540 650_7 $$099896-85-2$$2NLM Chemicals$$aarginyl-glycyl-aspartic acid
000032540 650_7 $$099896-88-5$$2NLM Chemicals$$aglycyl-arginyl-glycyl-glutamyl-seryl-proline
000032540 650_7 $$0EC 2.7.10.2$$2NLM Chemicals$$asrc-Family Kinases
000032540 650_7 $$0EC 2.7.11.24$$2NLM Chemicals$$aMitogen-Activated Protein Kinases
000032540 650_7 $$0EC 2.7.11.24$$2NLM Chemicals$$ap38 Mitogen-Activated Protein Kinases
000032540 650_7 $$2WoSType$$aJ
000032540 7001_ $$0P:(DE-HGF)0$$aSchliess, F.$$b1
000032540 7001_ $$0P:(DE-HGF)0$$aReissmann, R.$$b2
000032540 7001_ $$0P:(DE-HGF)0$$aGörg, B.$$b3
000032540 7001_ $$0P:(DE-Juel1)131988$$aWeiergräber, O.$$b4$$uFZJ
000032540 7001_ $$0P:(DE-HGF)0$$aKocalkova, M.$$b5
000032540 7001_ $$0P:(DE-HGF)0$$aDombrowski, F.$$b6
000032540 7001_ $$0P:(DE-HGF)0$$aHäussinger, D.$$b7
000032540 773__ $$0PERI:(DE-600)1474604-9$$a10.1074/jbc.M210699200$$gVol. 278, p. 27088 - 27095$$p27088 - 27095$$q278<27088 - 27095$$tThe @journal of biological chemistry$$v278$$x0021-9258$$y2003
000032540 8567_ $$uhttp://hdl.handle.net/2128/2651$$uhttp://dx.doi.org/10.1074/jbc.M210699200
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000032540 9201_ $$0I:(DE-Juel1)VDB58$$d31.12.2006$$gIBI$$kIBI-2$$lBiologische Strukturforschung$$x0
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