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@ARTICLE{vomDahl:32540,
author = {vom Dahl, S. and Schliess, F. and Reissmann, R. and Görg,
B. and Weiergräber, O. and Kocalkova, M. and Dombrowski, F.
and Häussinger, D.},
title = {{I}nvolvement of integrins in osmosensing and signaling
towards autophagic proteolysis in rat liver},
journal = {The journal of biological chemistry},
volume = {278},
issn = {0021-9258},
address = {Bethesda, Md.},
publisher = {Soc.},
reportid = {PreJuSER-32540},
pages = {27088 - 27095},
year = {2003},
note = {Record converted from VDB: 12.11.2012},
abstract = {Inhibition 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.},
keywords = {Animals / Autophagy / Cell Size: drug effects / Cell Size:
physiology / Cells, Cultured / Hepatocytes: cytology /
Hepatocytes: drug effects / Hepatocytes: physiology /
Integrins: antagonists $\&$ inhibitors / Integrins:
physiology / Liver: drug effects / Liver: physiology /
Liver: ultrastructure / MAP Kinase Signaling System / Male /
Mitogen-Activated Protein Kinases: metabolism / Models,
Biological / Oligopeptides: pharmacology / Perfusion / Rats
/ Rats, Wistar / Signal Transduction / Water-Electrolyte
Balance: physiology / p38 Mitogen-Activated Protein Kinases
/ src-Family Kinases: antagonists $\&$ inhibitors /
src-Family Kinases: metabolism / Integrins (NLM Chemicals) /
Oligopeptides (NLM Chemicals) /
glycyl-arginyl-glycyl-aspartyl-seryl-proline (NLM Chemicals)
/ arginyl-glycyl-aspartic acid (NLM Chemicals) /
glycyl-arginyl-glycyl-glutamyl-seryl-proline (NLM Chemicals)
/ src-Family Kinases (NLM Chemicals) / Mitogen-Activated
Protein Kinases (NLM Chemicals) / p38 Mitogen-Activated
Protein Kinases (NLM Chemicals) / J (WoSType)},
cin = {IBI-2},
ddc = {570},
cid = {I:(DE-Juel1)VDB58},
pnm = {Neurowissenschaften},
pid = {G:(DE-Juel1)FUEK255},
shelfmark = {Biochemistry $\&$ Molecular Biology},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:12721289},
UT = {WOS:000184155700102},
doi = {10.1074/jbc.M210699200},
url = {https://juser.fz-juelich.de/record/32540},
}