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| Verfasst von: | Kemmer, Isabel M. [VerfasserIn]  |
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| | Nava, Michele M. [VerfasserIn] |
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| | Wickström, Sara A. [VerfasserIn] |
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| | Gräter, Frauke [VerfasserIn] |
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| Titel: | ATP allosterically stabilizes integrin-linked kinase for efficient force generation |
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| Verf.angabe: | Isabel M. Martin, Michele M. Nava, Sara A. Wickström, and Frauke Gräter |
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| E-Jahr: | 2022 |
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| Jahr: | March 8, 2022 |
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| Umfang: | 11 S. |
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| Fussnoten: | Gesehen am 19.12.2022 |
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| Titel Quelle: | Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America |
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| Ort Quelle: | Washington, DC : National Acad. of Sciences, 1915 |
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| Jahr Quelle: | 2022 |
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| Band/Heft Quelle: | 119(2022), 11, Artikel-ID e2106098119, Seite 1-11 |
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| ISSN Quelle: | 1091-6490 |
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| Abstract: | Focal adhesions link the actomyosin cytoskeleton to the extracellular matrix regulating cell adhesion, shape, and migration. Adhesions are dynamically assembled and disassembled in response to extrinsic and intrinsic forces, but how the essential adhesion component integrin-linked kinase (ILK) dynamically responds to mechanical force and what role adenosine triphosphate (ATP) bound to this pseudokinase plays remain elusive. Here, we apply force-probe molecular-dynamics simulations of human ILK:alpha-parvin coupled to traction force microscopy to explore ILK mechanotransducing functions. We identify two key salt-bridge-forming arginines within the allosteric, ATP-dependent force-propagation network of ILK. Disrupting this network by mutation impedes parvin binding, focal adhesion stabilization, force generation, and thus migration. Under tension, ATP shifts the balance from rupture of the complex to protein unfolding, indicating that ATP increases the force threshold required for focal adhesion disassembly. Our study proposes a role of ATP as an obligatory binding partner for structural and mechanical integrity of the pseudokinase ILK, ensuring efficient cellular force generation and migration. |
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| DOI: | doi:10.1073/pnas.2106098119 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext ; Verlag: https://doi.org/10.1073/pnas.2106098119 |
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| | kostenfrei: Volltext: https://www.pnas.org/doi/full/10.1073/pnas.2106098119 |
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| | DOI: https://doi.org/10.1073/pnas.2106098119 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | alpha-parvin |
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| | binding |
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| | cell-adhesion |
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| | domain |
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| | focal adhesion |
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| | ilk |
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| | integrin-linked kinase |
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| | kindlin-2 |
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| | localization |
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| | molecular dynamics |
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| | pinch |
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| | structural basis |
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| | therapeutic target |
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| | traction force microscopy |
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| K10plus-PPN: | 1827879262 |
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| Verknüpfungen: | → Zeitschrift |
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ATP allosterically stabilizes integrin-linked kinase for efficient force generation / Kemmer, Isabel M. [VerfasserIn]; March 8, 2022 (Online-Ressource)
