title: Improvement of insulin signaling in myoblast cells by an addition of SKIP-binding peptide within Pak1 kinase domain.
abstract: Abnormalities in insulin-induced glucose incorporation in skeletal muscle were observed in Type 2 diabetes. Our previous studies revealed that the binding between skeletal muscle and kidney-enriched inositol polyphosphate phosphatase (SKIP) and p21-activated protein kinase (Pak1) at the plasma membrane is induced insulin-dependently and that this binding mediated a rapid and efficient termination of insulin signaling and a subsequent glucose uptake into skeletal muscle cells. Here, we identified 11-amino-acids peptide within kinase domain of Pak1, necessary and sufficient for SKIP binding. Expression of this region in C2C12 cells resulted in an increase in insulin signaling. Supplementation of a synthetic peptide of this sequence increased insulin signaling and insulin-induced glucose uptake into skeletal muscle cell lines. These findings suggest the physiological role of Pak1-SKIP binding in the regulation of insulin signaling in skeletal muscle.
authors.affiliation: The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki, Kobe 650-0017, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ijuin
authors.affiliation: The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki, Kobe 650-0017, Japan. Electronic address: Takenawa@med.kobe-u.ac.jp.
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Takenawa
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D032446:Myoblasts / Q000166:cytology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D020349:Surface Plasmon Resonance; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D007328:Insulin; D011994:Recombinant Proteins; C515905:Pak1 protein, mouse; D054462:p21-Activated Kinases; C531212:Pps protein, mouse; D010744:Phosphoric Monoester Hydrolases; D005947:Glucose
keywords: Insulin signaling; Pak1; SKIP; Skeletal muscle