%0 Journal Article %1 reimannPhosphoproteomicsIdentifiesDualsite2020a %A Reimann, Lena %A Schwäble, Anja N. %A Fricke, Anna L. %A Mühlhäuser, Wignand W. D. %A Leber, Yvonne %A Lohanadan, Keerthika %A Puchinger, Martin G. %A Schäuble, Sascha %A Faessler, Erik %A Wiese, Heike %A Reichenbach, Christa %A Knapp, Bettina %A Peikert, Christian D. %A Drepper, Friedel %A Hahn, Udo %A Kreutz, Clemens %A van der Ven, Peter F. M. %A Radziwill, Gerald %A Djinović-Carugo, Kristina %A Fürst, Dieter O. %A Warscheid, Bettina %C England %D 2020 %J Communications biology %K 3-Kinases/metabolism,Phosphoproteins/*metabolism,Phosphorylation,Protein Acid Amino Binding,Proteolysis,Proteome/analysis/*metabolism,Proto-Oncogene Cells,Humans,Muscle Development,Muscle Fibers Motifs,Carrier Proteins Proteins/*metabolism,Cytoskeletal Proteins/*metabolism,Filamins/*metabolism,HEK293 Skeletal/cytology/*metabolism,Phosphatidylinositol Transduction,to_read c-akt/metabolism,Signal %N 1 %P 253 %R 10.1038/s42003-020-0982-5 %T Phosphoproteomics Identifies Dual-Site Phosphorylation in an Extended Basophilic Motif Regulating FILIP1-mediated Degradation of Filamin-C. %V 3 %X The PI3K/Akt pathway promotes skeletal muscle growth and myogenic differentiation. Although its importance in skeletal muscle biology is well documented, many of its substrates remain to be identified. We here studied PI3K/Akt signaling in contracting skeletal muscle cells by quantitative phosphoproteomics. We identified the extended basophilic phosphosite motif RxRxxpS/TxxpS/T in various proteins including filamin-C (FLNc). Importantly, this extended motif, located in a unique insert in Ig-like domain 20 of FLNc, is doubly phosphorylated. The protein kinases responsible for this dual-site phosphorylation are Akt and PKC$\alpha$. Proximity proteomics and interaction analysis identified filamin A-interacting protein 1 (FILIP1) as direct FLNc binding partner. FILIP1 binding induces filamin degradation, thereby negatively regulating its function. Here, dual-site phosphorylation of FLNc not only reduces FILIP1 binding, providing a mechanism to shield FLNc from FILIP1-mediated degradation, but also enables fast dynamics of FLNc necessary for its function as signaling adaptor in cross-striated muscle cells.

@article{reimannPhosphoproteomicsIdentifiesDualsite2020a, abstract = {The PI3K/Akt pathway promotes skeletal muscle growth and myogenic differentiation. Although its importance in skeletal muscle biology is well documented, many of its substrates remain to be identified. We here studied PI3K/Akt signaling in contracting skeletal muscle cells by quantitative phosphoproteomics. We identified the extended basophilic phosphosite motif RxRxxp[S/T]xxp[S/T] in various proteins including filamin-C (FLNc). Importantly, this extended motif, located in a unique insert in Ig-like domain 20 of FLNc, is doubly phosphorylated. The protein kinases responsible for this dual-site phosphorylation are Akt and PKC{$\alpha$}. Proximity proteomics and interaction analysis identified filamin A-interacting protein 1 (FILIP1) as direct FLNc binding partner. FILIP1 binding induces filamin degradation, thereby negatively regulating its function. Here, dual-site phosphorylation of FLNc not only reduces FILIP1 binding, providing a mechanism to shield FLNc from FILIP1-mediated degradation, but also enables fast dynamics of FLNc necessary for its function as signaling adaptor in cross-striated muscle cells.}, added-at = {2024-05-17T13:01:35.000+0200}, address = {England}, author = {Reimann, Lena and Schw{\"a}ble, Anja N. and Fricke, Anna L. and M{\"u}hlh{\"a}user, Wignand W. D. and Leber, Yvonne and Lohanadan, Keerthika and Puchinger, Martin G. and Sch{\"a}uble, Sascha and Faessler, Erik and Wiese, Heike and Reichenbach, Christa and Knapp, Bettina and Peikert, Christian D. and Drepper, Friedel and Hahn, Udo and Kreutz, Clemens and {van der Ven}, Peter F. M. and Radziwill, Gerald and {Djinovi{\'c}-Carugo}, Kristina and F{\"u}rst, Dieter O. and Warscheid, Bettina}, biburl = {https://www.bibsonomy.org/bibtex/2a64ffa19484d81e2a618a18b47b34dfd/warscheidlab}, doi = {10.1038/s42003-020-0982-5}, interhash = {91eeeb89ffb3e82d26a5b7578ad82e37}, intrahash = {a64ffa19484d81e2a618a18b47b34dfd}, issn = {2399-3642}, journal = {Communications biology}, keywords = {3-Kinases/metabolism,Phosphoproteins/*metabolism,Phosphorylation,Protein Acid Amino Binding,Proteolysis,Proteome/analysis/*metabolism,Proto-Oncogene Cells,Humans,Muscle Development,Muscle Fibers Motifs,Carrier Proteins Proteins/*metabolism,Cytoskeletal Proteins/*metabolism,Filamins/*metabolism,HEK293 Skeletal/cytology/*metabolism,Phosphatidylinositol Transduction,to_read c-akt/metabolism,Signal}, langid = {english}, month = may, number = 1, pages = 253, pmcid = {PMC7244511}, pmid = {32444788}, timestamp = {2024-05-17T13:01:35.000+0200}, title = {Phosphoproteomics Identifies Dual-Site Phosphorylation in an Extended Basophilic Motif Regulating {{FILIP1-mediated}} Degradation of Filamin-{{C}}.}, volume = 3, year = 2020 }