title: Exercise-induced phosphorylation of the novel Akt substrates AS160 and filamin A in human skeletal muscle.
abstract: Skeletal muscle contraction stimulates multiple signaling cascades that govern a variety of metabolic and transcriptional events. Akt/protein kinase B regulates metabolism and growth/muscle hypertrophy, but contraction effects on this target and its substrates are varied and may depend on the mode of the contractile stimulus. Accordingly, we determined the effects of endurance or resistance exercise on phosphorylation of Akt and downstream substrates in six trained cyclists who performed a single bout of endurance or resistance exercise separated by approximately 7 days. Muscle biopsies were taken from the vastus lateralis at rest and immediately after exercise. Akt Ser(473) phosphorylation was increased (1.8-fold; P=0.011) after endurance but was unchanged after resistance exercise. Conversely, Akt Thr(308) phosphorylation was unaltered after either bout of exercise. Several exercise-responsive phosphoproteins were detected by immunoblot analysis with a phospho-Akt substrate antibody. pp160 and pp300 were identified as AS160 and filamin A, respectively, with increased phosphorylation (2.0- and 4.9-fold, respectively; P<0.05) after endurance but not resistance exercise. In conclusion, AS160 and filamin A may provide an important link to mediate endurance exercise-induced bioeffects in skeletal muscle.
authors.affiliation: Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden.
authors.forename: Atul
authors.initials: A
authors.lastname: Deshmukh
authors.forename: Vernon G
authors.initials: VG
authors.lastname: Coffey
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhong
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Chibalin
authors.forename: John A
authors.initials: JA
authors.lastname: Hawley
authors.forename: Juleen R
authors.initials: JR
authors.lastname: Zierath
mesh_terms: D000328:Adult; D003285:Contractile Proteins / Q000378:metabolism*; D018592:Cross-Over Studies; D004591:Electrophoresis, Polyacrylamide Gel; D015444:Exercise / Q000502:physiology*; D064448:Filamins; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D020690:GTPase-Activating Proteins; D008840:Microfilament Proteins; C518767:TBC1D4 protein, human; D051057:Proto-Oncogene Proteins c-akt