FLNc S2233 S2236 PRM analysis

ABSTRACT: Skeletal muscle is known to adapt dynamically to changes in workload by regulatory processes of the phosphatidylinositide 3-kinase (PI3K)/Akt pathway. We performed a global quantitative phosphoproteomics analysis of contracting mouse C2 myotubes treated with insulin growth factor 1 (IGF-1) or LY294002 to activate or inhibit PI3K/Akt signaling, respectively. Among the significantly regulated phosphopeptides we identified the novel extended basophilic motif RxRxxp[S/T]xxp[S] to be enriched in the set of down-regulated phosphopeptides following inhibition of PI3K/Akt signaling. Using literature-based text mining we identified the kinases Akt, serum and glucocorticoid-regulated kinase 1 (SGK1) and p70S6 kinase to be potentially involved in the phosphorylation of the first serine in the RxRxxp[S/T]xxp[S] motif, whereas no kinase targeting the serine in the +3 position was revealed. In the signaling adapter protein filamin c (FLNc) we found this novel motif in immunoglobulin (Ig)-like domain 20 which is involved in various protein interactions. Through in vitro and in cellulo kinase assays we identified Akt and protein kinase C alpha as the responsible kinases phosphorylating FLNc in this motif at the first and the second serine, respectively.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Skeletal Muscle Myoblast, Myoblast Cell Line

SUBMITTER: Friedel Drepper  

LAB HEAD: Bettina Warscheid

PROVIDER: PXD009228 | Pride | 2020-06-30

REPOSITORIES: Pride