Protein arginine methylation regulates insulin signaling in L6 skeletal muscle cells
Protein arginine methylation regulates insulin signaling in L6 skeletal muscle cells
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DOI：
10.1016/j.bbrc.2007.10.113
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发表时间：
2007-12-28
影响因子：
3.1
通讯作者：
Yada, Toshihiko
中科院分区：
文献类型：
--
作者：
Iwasaki, Hiroaki;Yada, Toshihiko
蛋白N-精氨酸甲基转移酶（PRMT）1催化多种底物中的精氨酸甲基化，尽管PRMT 1在胰岛素作用中的潜在作用尚未确定。因此，我们研究了PRMT 1介导的甲基化对骨骼L 6肌管中胰岛素信号传导和葡萄糖摄取的影响。暴露于胰岛素的L 6肌管迅速诱导PRMT 1易位，并增加其在膜组分中的催化活性。膜组分中的几种蛋白质在胰岛素处理后被甲基化，这通过用甲基转移酶抑制剂5 '-脱氧-5'-（甲硫基）腺苷（MTA）或针对PRMT 1的小干扰RNA（PRMT 1-siRNA）预处理来抑制。用MTA或PRMT 1-siRNA抑制精氨酸甲基化减少了胰岛素刺激的胰岛素受体（IR）β和IRS-1酪氨酸磷酸化的后期，IRS-I与P13-K的p85 α亚基的结合，以及葡萄糖摄取。我们的研究结果表明，PRMT 1介导的甲基化作为一个积极的调节IR/IRS-1/P13-K途径和随后的葡萄糖摄取骨骼肌细胞。(C)2007年爱思唯尔公司All rights reserved.
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-I with p85 alpha subunit of P13-K, and glucose uptake. Our results suggest that PRMT1-mediated methylation serves as a positive modulator of IR/IRS-1/P13-K pathway and subsequent glucose uptake in skeletal muscle cells. (C) 2007 Elsevier Inc. All rights reserved.