Protein phosphatase-1 regulates the binding of filamin C to FILIP1 in cultured skeletal muscle cells under mechanical stress.

Autor: Kokot T; Integrative Signaling Research, Institute of Biology III, University of Freiburg, Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany., Zimmermann JP; Biochemistry II, Theodor-Boveri-Institut, Biozentrum, Faculty of Chemistry and Pharmacy, University of Würzburg, Würzburg, Germany., Schwäble AN; Biochemistry - Functional Proteomics, Institute of Biology II, University of Freiburg, Freiburg, Germany.; Current address: Celonic AG, Basel, Switzerland., Reimann L; Biochemistry - Functional Proteomics, Institute of Biology II, University of Freiburg, Freiburg, Germany.; Current address: Celonic AG, Basel, Switzerland., Herr AL; Biochemistry - Functional Proteomics, Institute of Biology II, University of Freiburg, Freiburg, Germany.; Current address: Sartorius CellGenix GmbH, Freiburg, Germany., Höfflin N; Integrative Signaling Research, Institute of Biology III, University of Freiburg, Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany., Köhn M; Integrative Signaling Research, Institute of Biology III, University of Freiburg, Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany., Warscheid B; Biochemistry II, Theodor-Boveri-Institut, Biozentrum, Faculty of Chemistry and Pharmacy, University of Würzburg, Würzburg, Germany. bettina.warscheid@uni-wuerzburg.de.; Biochemistry - Functional Proteomics, Institute of Biology II, University of Freiburg, Freiburg, Germany. bettina.warscheid@uni-wuerzburg.de.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Nov 09; Vol. 14 (1), pp. 27348. Date of Electronic Publication: 2024 Nov 09.
DOI: 10.1038/s41598-024-78953-8
Abstrakt: The actin-binding protein filamin c (FLNc) is a key mediator in the response of skeletal muscle cells to mechanical stress. In addition to its function as a structural scaffold, FLNc acts as a signaling adaptor which is phosphorylated at S2234 in its mechanosensitive domain 20 (d20) through AKT. Here, we discovered a strong dephosphorylation of FLNc-pS2234 in cultured skeletal myotubes under acute mechanical stress, despite high AKT activity. We found that all three protein phosphatase 1 (PP1) isoforms are part of the FLNc d18-21 interactome. Enzymatic assays demonstrate that PP1 efficiently dephosphorylates FLNc-pS2234 and in vitro and in cells upon PP1 activation using specific modulators. FLNc-pS2234 dephosphorylation promotes the interaction with FILIP1, a mediator for filamin degradation. Altogether, we present a model in which dephosphorylation of FLNc d20 by the dominant action of PP1c prevails over AKT activity to promote the binding of the filamin degradation-inducing factor FILIP1 during acute mechanical stress.
(© 2024. The Author(s).)
Databáze: MEDLINE
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