Identification of filamin C as a new physiological substrate of PKβα using KESTREL

James T. Murray (Lead / Corresponding author), David G. Campbell, Mark Peggie, Mora Alfonso, Philip Cohen

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    35 Citations (Scopus)

    Abstract

    We detected a protein in rabbit skeletal muscle extracts that was phosphorylated rapidly by PKBα (protein kinase Bα), but not by SGK1 (serum- and glucocorticoid-induced kinase 1), and identified it as the cytoskeletal protein FLNc (filamin C). PKBα phosphorylated FLNc at Ser2213 in vitro, which lies in an insert not present in the FLNa and FLNb isoforms. Ser2213 became phosphorylated when C2C12 myoblasts were stimulated with insulin or epidermal growth factor, and phosphorylation was prevented by low concentrations of wortmannin, at which it is a relatively specific inhibitor of phosphoinositide 3-kinase. PD 184352 [an inhibitor of the classical MAPK (mitogen-activated protein kinase) cascade] and/or rapamycin [an inhibitor of mTOR (mammalian target of rapamycin)] had no effect. Insulin also induced the phosphorylation of FLNc at Ser2213 in cardiac muscle in vivo, but not in cardiac muscle that does not express PDK1 (3-phosphoinositide- dependent kinase 1), the upstream activator of PKB. These results identify the muscle-specific isoform FLNc as a new physiological substrate for PKB.

    Original languageEnglish
    Pages (from-to)489-494
    Number of pages6
    JournalBiochemical Journal
    Volume384
    Issue number3
    DOIs
    Publication statusPublished - 15 Dec 2004

    Keywords

    • Cytoskeleton
    • Filamin
    • Kinase substrate tracking and elucidation (KESTREL)
    • Phosphorylation
    • Protein kinase B (PKB)

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