Involvement of PRMT1 in hnRNPQ activation and internalization of insulin receptor.
Insulin signaling in skeletal L6 myotubes is known to be affected by arginine methylation catalyzed by protein N-arginine methyltransferase 1 (PRMT1), however, the mechanism by which this occurs has not yet been defined. This study aimed to determine the exact substrate involved in the methylation and regulating insulin signaling in cells. Insulin enhanced arginine methylation of a 66-kDa protein (p66) concomitant with translocation of PRMT1 to the membrane fraction. Peptide mass fingerprinting identified p66 as a heterogeneous nuclear ribonucleoprotein, hnRNPQ that was bound to and methylated by PRMT1. Pharmacological inhibition of methylation (MTA) and small interfering RNA against PRMT1 (PRMT1-siRNA) attenuated insulin-stimulated tyrosine phosphorylation of hnRNPQ and insulin receptor (IR), and the interaction between hnRNPQ and IR. MTA, PRMT1-siRNA, and hnRNPQ-siRNA inhibited internalization of IR in the same manner. These data suggest that the PRMT1-mediated methylation of hnRNPQ is implicated in IR trafficking and insulin signaling in skeletal L6 myotubes.
Iwasaki
Hiroaki
H
Division of Endocrinology and Metabolism, Department of Internal Medicine, Toshiba Rinkan Hospital, 7-9-1 Kami-tsuruma, Sagamihara, Kanagawa 228-8585, Japan. hiwasaki-dm@umin.net
D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D008745:Methylation / Q000187:drug effects; D008969:Molecular Sequence Data; D032446:Myoblasts / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D034441:Heterogeneous-Nuclear Ribonucleoproteins; D007328:Insulin; D034741:RNA, Small Interfering; C530621:hnRNPQ protein, rat; D014443:Tyrosine; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases; D011972:Receptor, Insulin