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000006381 0247_ $$2DOI$$a10.1074/jbc.M806825200
000006381 0247_ $$2WOS$$aWOS:000264892900056
000006381 037__ $$aPreJuSER-6381
000006381 041__ $$aeng
000006381 082__ $$a570
000006381 084__ $$2WoS$$aBiochemistry & Molecular Biology
000006381 1001_ $$0P:(DE-Juel1)VDB71076$$aWaschbüsch, D.$$b0$$uFZJ
000006381 245__ $$aPresenilin 1 affects focal adhesion site formation and cell force generation via c-Src transcriptional and posttranslational regulation
000006381 260__ $$aBethesda, Md.$$bSoc.$$c2009
000006381 300__ $$a
000006381 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
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000006381 3367_ $$2BibTeX$$aARTICLE
000006381 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000006381 3367_ $$2DRIVER$$aarticle
000006381 440_0 $$03091$$aJournal of Biological Chemistry$$v284$$x0021-9258$$y10138 - 10149
000006381 500__ $$aThis work was supported by Deutsche Forschungsgemeinschaft Sonderforschungsbereich 645. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact.
000006381 520__ $$aPresenilin 1 and 2 (PS) are critical components of the gamma-secretase complex that cleaves type I transmembrane proteins within their transmembrane domains. This process leads to release of proteolytically processed products from cellular membranes and plays an essential role in signal transduction or vital functions as cell adhesion. Here we studied the function of presenilins in cell-matrix interaction of wild-type and PS knock-out mouse embryonic fibroblasts. We found for PS1(-/-) cells an altered morphology with significantly reduced sizes of focal adhesion sites compared with wild type. Cell force analyses on micropatterned elastomer films revealed PS1(-/-) cell forces to be reduced by 50%. Pharmacological inhibition confirmed this function of gamma-secretase in adhesion site and cell force formation. On the regulatory level, PS1 deficiency was associated with strongly decreased phosphotyrosine levels of focal adhesion site-specific proteins. The reduced tyrosine phosphorylation was caused by a down-regulation of c-Src kinase activity primarily at the level of c-Src transcription. The direct regulatory connection between PS1 and c-Src could be identified with ephrinB2 as PS1 target protein. Overexpression of ephrinB2 cytoplasmic domain resulted in its nuclear translocation with increased levels of c-Src and a full complementation of the PS1(-/-) adhesion and phosphorylation phenotype. Cleavage of full-length EB2 and subsequent intracellular domain translocation depended on PS1 as these processes were only found in WT cells. Therefore, we conclude that gamma-secretase is vital for controlling cell adhesion and force formation by transcriptional regulation of c-Src via ephrinB2 cleavage.
000006381 536__ $$0G:(DE-Juel1)FUEK414$$2G:(DE-HGF)$$aKondensierte Materie$$cP54$$x0
000006381 588__ $$aDataset connected to Web of Science, Pubmed
000006381 650_2 $$2MeSH$$aAnimals
000006381 650_2 $$2MeSH$$aCell Line
000006381 650_2 $$2MeSH$$aCytoplasm: metabolism
000006381 650_2 $$2MeSH$$aEphrin-B2: metabolism
000006381 650_2 $$2MeSH$$aFibroblasts: metabolism
000006381 650_2 $$2MeSH$$aFocal Adhesions
000006381 650_2 $$2MeSH$$aGene Expression Regulation
000006381 650_2 $$2MeSH$$aMice
000006381 650_2 $$2MeSH$$aMicroscopy, Fluorescence
000006381 650_2 $$2MeSH$$aModels, Biological
000006381 650_2 $$2MeSH$$aPhenotype
000006381 650_2 $$2MeSH$$aPresenilin-1: metabolism
000006381 650_2 $$2MeSH$$aProtein Processing, Post-Translational
000006381 650_2 $$2MeSH$$aTyrosine: chemistry
000006381 650_2 $$2MeSH$$asrc-Family Kinases: metabolism
000006381 650_7 $$00$$2NLM Chemicals$$aEphrin-B2
000006381 650_7 $$00$$2NLM Chemicals$$aPresenilin-1
000006381 650_7 $$055520-40-6$$2NLM Chemicals$$aTyrosine
000006381 650_7 $$0EC 2.7.10.2$$2NLM Chemicals$$asrc-Family Kinases
000006381 650_7 $$2WoSType$$aJ
000006381 7001_ $$0P:(DE-Juel1)161241$$aBorn, S.$$b1$$uFZJ
000006381 7001_ $$0P:(DE-Juel1)VDB84258$$aNiediek, V.$$b2$$uFZJ
000006381 7001_ $$0P:(DE-Juel1)VDB8902$$aKirchgeßner, N.$$b3$$uFZJ
000006381 7001_ $$0P:(DE-Juel1)VDB86854$$aTamboli, I.Y.$$b4$$uFZJ
000006381 7001_ $$0P:(DE-Juel1)VDB59679$$aWalter, J.$$b5$$uFZJ
000006381 7001_ $$0P:(DE-Juel1)128833$$aMerkel, R.$$b6$$uFZJ
000006381 7001_ $$0P:(DE-Juel1)VDB27696$$aHoffmann, B.$$b7$$uFZJ
000006381 773__ $$0PERI:(DE-600)1474604-9$$a10.1074/jbc.M806825200$$gVol. 284$$q284$$tThe @journal of biological chemistry$$v284$$x0021-9258$$y2009
000006381 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2665068
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