title: Protein arginine methylation regulates insulin signaling in L6 skeletal muscle cells.
abstract: Protein N-arginine methyltransferase (PRMT)1 catalyzes arginine methylation in a variety of substrates, although the potential role of PRMT1 in insulin action has not been defined. We therefore investigated the effect of PRMT1-mediated methylation on insulin signaling and glucose uptake in skeletal L6 myotubes. Exposure of L6 myotubes to insulin rapidly induced translocation of PRMT1 and increased its catalytic activity in membrane fraction. Several proteins in the membrane fraction were arginine-methylated after insulin treatment, which were inhibited by pretreatment with an inhibitor of methyltransferase, 5'-deoxy-5'-(methylthio)adenosine (MTA), or a small interfering RNA against PRMT1 (PRMT1-siRNA). Inhibition of arginine methylation with MTA or PRMT1-siRNA diminished later phase of insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) beta and IRS-1, association of IRS-1 with p85alpha subunit of PI3-K, and glucose uptake. Our results suggest that PRMT1-mediated methylation serves as a positive modulator of IR/IRS-1/PI3-K pathway and subsequent glucose uptake in skeletal muscle cells.
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University, School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
mesh_terms: D001120:Arginine / Q000378:metabolism*; D002460:Cell Line; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism*; D008745:Methylation / Q000187:drug effects; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D007328:Insulin; D012097:Repressor Proteins; D001120:Arginine; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases