Reference - Detail
| RRC ID | 60896 |
|---|---|
| Author | Reimann L, Schwäble AN, Fricke AL, Mühlhäuser WWD, Leber Y, Lohanadan K, Puchinger MG, Schäuble S, Faessler E, Wiese H, Reichenbach C, Knapp B, Peikert CD, Drepper F, Hahn U, Kreutz C, van der Ven PFM, Radziwill G, Djinović-Carugo K, Fürst DO, Warscheid B. |
| Title | Phosphoproteomics identifies dual-site phosphorylation in an extended basophilic motif regulating FILIP1-mediated degradation of filamin-C. |
| Journal | Commun Biol |
| 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 PKCα. 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. |
| Volume | 3(1) |
| Pages | 253 |
| Published | 2020-5-22 |
| DOI | 10.1038/s42003-020-0982-5 |
| PII | 10.1038/s42003-020-0982-5 |
| PMID | 32444788 |
| PMC | PMC7244511 |
| MeSH | Amino Acid Motifs Carrier Proteins / metabolism* Cytoskeletal Proteins / metabolism* Filamins / metabolism* HEK293 Cells Humans Muscle Development Muscle Fibers, Skeletal / cytology Muscle Fibers, Skeletal / metabolism* Phosphatidylinositol 3-Kinases / metabolism Phosphoproteins / metabolism* Phosphorylation Protein Binding Proteolysis Proteome / analysis Proteome / metabolism* Proto-Oncogene Proteins c-akt / metabolism Signal Transduction |
| IF | 4.165 |
| Times Cited | 0 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | NRCD human cDNA clones (RDB06607) ARi57A02 (HKR182802) |