title: Myosin 5a is an insulin-stimulated Akt2 (protein kinase Bbeta) substrate modulating GLUT4 vesicle translocation.
abstract: Phosphatidylinositol 3-kinase activation of Akt signaling is critical to insulin-stimulated glucose transport and GLUT4 translocation. However, the downstream signaling events following Akt activation which mediate glucose transport stimulation remain relatively unknown. Here we identify an Akt consensus phosphorylation motif in the actin-based motor protein myosin 5a and show that insulin stimulation leads to phosphorylation of myosin 5a at serine 1650. This Akt-mediated phosphorylation event enhances the ability of myosin 5a to interact with the actin cytoskeleton. Small interfering RNA-induced inhibition of myosin 5a and expression of dominant-negative myosin 5a attenuate insulin-stimulated glucose transport and GLUT4 translocation. Furthermore, knockdown of Akt2 or expression of dominant-negative Akt (DN-Akt) abolished insulin-stimulated phosphorylation of myosin 5a, inhibited myosin 5a binding to actin, and blocked insulin-stimulated glucose transport. Taken together, these data indicate that myosin 5a is a newly identified direct substrate of Akt2 and, upon insulin stimulation, phosphorylated myosin 5a facilitates anterograde movement of GLUT4 vesicles along actin to the cell surface.
authors.affiliation: Department of Medicine (0673), University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0673, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshizaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Imamura
authors.forename: Jennie L
authors.initials: JL
authors.lastname: Babendure
authors.forename: Juu-Chin
authors.initials: JC
authors.lastname: Lu
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sonoda
authors.forename: Jerrold M
authors.initials: JM
authors.lastname: Olefsky
mesh_terms: D041721:3T3-L1 Cells; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005799:Genes, Dominant; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000378:metabolism*; D024701:Myosin Type V / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D013379:Substrate Specificity / Q000187:drug effects; D022161:Transport Vesicles / Q000187:drug effects* / Q000378:metabolism*; D020695:rab4 GTP-Binding Proteins / Q000378:metabolism; D000099293:Protein Kinase C-lambda
chemical_list: D000199:Actins; D005947:Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D007527:Isoenzymes; D018995:Myosin Heavy Chains; D024701:Myosin Type V; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D020695:rab4 GTP-Binding Proteins; D000099293:Protein Kinase C-lambda; C513082:Myo5a protein, mouse; C494922:Akt2 protein, mouse