Hauptseite > Publikationsdatenbank > Presenilin 1 affects focal adhesion site formation and cell force generation via c-Src transcriptional and posttranslational regulation > print

001     6381
005     20200402205701.0
024 7 _ |2 pmid
|a pmid:19176482
024 7 _ |2 pmc
|a pmc:PMC2665068
024 7 _ |2 DOI
|a 10.1074/jbc.M806825200
024 7 _ |2 WOS
|a WOS:000264892900056
037 _ _ |a PreJuSER-6381
041 _ _ |a eng
082 _ _ |a 570
084 _ _ |2 WoS
|a Biochemistry & Molecular Biology
100 1 _ |a Waschbüsch, D.
|b 0
|u FZJ
|0 P:(DE-Juel1)VDB71076
245 _ _ |a Presenilin 1 affects focal adhesion site formation and cell force generation via c-Src transcriptional and posttranslational regulation
260 _ _ |a Bethesda, Md.
|b Soc.
|c 2009
300 _ _ |a
336 7 _ |a Journal Article
|0 PUB:(DE-HGF)16
|2 PUB:(DE-HGF)
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|0 0
|2 EndNote
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a article
|2 DRIVER
440 _ 0 |a Journal of Biological Chemistry
|x 0021-9258
|0 3091
|y 10138 - 10149
|v 284
500 _ _ |a This 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.
520 _ _ |a Presenilin 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.
536 _ _ |a Kondensierte Materie
|c P54
|2 G:(DE-HGF)
|0 G:(DE-Juel1)FUEK414
|x 0
588 _ _ |a Dataset connected to Web of Science, Pubmed
650 _ 2 |2 MeSH
|a Animals
650 _ 2 |2 MeSH
|a Cell Line
650 _ 2 |2 MeSH
|a Cytoplasm: metabolism
650 _ 2 |2 MeSH
|a Ephrin-B2: metabolism
650 _ 2 |2 MeSH
|a Fibroblasts: metabolism
650 _ 2 |2 MeSH
|a Focal Adhesions
650 _ 2 |2 MeSH
|a Gene Expression Regulation
650 _ 2 |2 MeSH
|a Mice
650 _ 2 |2 MeSH
|a Microscopy, Fluorescence
650 _ 2 |2 MeSH
|a Models, Biological
650 _ 2 |2 MeSH
|a Phenotype
650 _ 2 |2 MeSH
|a Presenilin-1: metabolism
650 _ 2 |2 MeSH
|a Protein Processing, Post-Translational
650 _ 2 |2 MeSH
|a Tyrosine: chemistry
650 _ 2 |2 MeSH
|a src-Family Kinases: metabolism
650 _ 7 |0 0
|2 NLM Chemicals
|a Ephrin-B2
650 _ 7 |0 0
|2 NLM Chemicals
|a Presenilin-1
650 _ 7 |0 55520-40-6
|2 NLM Chemicals
|a Tyrosine
650 _ 7 |0 EC 2.7.10.2
|2 NLM Chemicals
|a src-Family Kinases
650 _ 7 |a J
|2 WoSType
700 1 _ |a Born, S.
|b 1
|u FZJ
|0 P:(DE-Juel1)161241
700 1 _ |a Niediek, V.
|b 2
|u FZJ
|0 P:(DE-Juel1)VDB84258
700 1 _ |a Kirchgeßner, N.
|b 3
|u FZJ
|0 P:(DE-Juel1)VDB8902
700 1 _ |a Tamboli, I.Y.
|b 4
|u FZJ
|0 P:(DE-Juel1)VDB86854
700 1 _ |a Walter, J.
|b 5
|u FZJ
|0 P:(DE-Juel1)VDB59679
700 1 _ |a Merkel, R.
|b 6
|u FZJ
|0 P:(DE-Juel1)128833
700 1 _ |a Hoffmann, B.
|b 7
|u FZJ
|0 P:(DE-Juel1)VDB27696
773 _ _ |a 10.1074/jbc.M806825200
|g Vol. 284
|q 284
|0 PERI:(DE-600)1474604-9
|t The @journal of biological chemistry
|v 284
|y 2009
|x 0021-9258
856 7 _ |2 Pubmed Central
|u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2665068
909 C O |o oai:juser.fz-juelich.de:6381
|p VDB
913 1 _ |k P54
|v Kondensierte Materie
|l Kondensierte Materie
|b Materie
|z entfällt bis 2009
|0 G:(DE-Juel1)FUEK414
|x 0
914 1 _ |y 2009
915 _ _ |0 StatID:(DE-HGF)0010
|a JCR/ISI refereed
920 1 _ |k IBN-4
|l Biomechanik
|d 31.12.2010
|g IBN
|0 I:(DE-Juel1)VDB802
|x 0
970 _ _ |a VDB:(DE-Juel1)114648
980 _ _ |a VDB
980 _ _ |a ConvertedRecord
980 _ _ |a journal
980 _ _ |a I:(DE-Juel1)ICS-7-20110106
980 _ _ |a UNRESTRICTED
981 _ _ |a I:(DE-Juel1)IBI-2-20200312
981 _ _ |a I:(DE-Juel1)ICS-7-20110106

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