PMID- 27739494 OWN - NLM STAT- MEDLINE DCOM- 20180411 LR - 20211103 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Oct 14 TI - A novel IRS-1-associated protein, DGKzeta regulates GLUT4 translocation in 3T3-L1 adipocytes. PG - 35438 LID - 10.1038/srep35438 [doi] LID - 35438 AB - Insulin receptor substrates (IRSs) are major targets of insulin receptor tyrosine kinases. Here we identified diacylglycerol kinase zeta (DGKzeta) as an IRS-1-associated protein, and examined roles of DGKzeta in glucose transporter 4 (GLUT4) translocation to the plasma membrane. When DGKzeta was knocked-down in 3T3-L1 adipocytes, insulin-induced GLUT4 translocation was inhibited without affecting other mediators of insulin-dependent signaling. Similarly, knockdown of phosphatidylinositol 4-phosphate 5-kinase 1alpha (PIP5K1alpha), which had been reported to interact with DGKzeta, also inhibited insulin-induced GLUT4 translocation. Moreover, DGKzeta interacted with IRS-1 without insulin stimulation, but insulin stimulation decreased this interaction. Over-expression of sDGKzeta (short-form DGKzeta), which competed out DGKzeta from IRS-1, enhanced GLUT4 translocation without insulin stimulation. Taking these results together with the data showing that cellular PIP5K activity was correlated with GLUT4 translocation ability, we concluded that IRS-1-associated DGKzeta prevents GLUT4 translocation in the absence of insulin and that the DGKzeta dissociated from IRS-1 by insulin stimulation enhances GLUT4 translocation through PIP5K1alpha activity. FAU - Liu, TingYu AU - Liu T AD - Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan. FAU - Yu, BuChin AU - Yu B AD - Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan. FAU - Kakino, Mamoru AU - Kakino M AD - Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan. FAU - Fujimoto, Hitoshi AU - Fujimoto H AD - Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan. FAU - Ando, Yasutoshi AU - Ando Y AD - Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan. FAU - Hakuno, Fumihiko AU - Hakuno F AD - Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan. FAU - Takahashi, Shin-Ichiro AU - Takahashi SI AD - Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161014 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Glucose Transporter Type 4) RN - 0 (Insulin) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (Irs1 protein, mouse) RN - 0 (Slc2a4 protein, mouse) RN - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)) RN - EC 2.7.1.107 (Diacylglycerol Kinase) RN - EC 2.7.1.107 (diacylglycerol kinase zeta, mouse) RN - EC 2.7.1.68 (1-phosphatidylinositol-4-phosphate 5-kinase) SB - IM MH - 3T3 Cells MH - Adipocytes/drug effects/*metabolism MH - Animals MH - CHO Cells MH - Cell Membrane/metabolism MH - Cricetinae MH - Cricetulus MH - Diacylglycerol Kinase/genetics/*metabolism MH - Glucose Transporter Type 4/*metabolism MH - HEK293 Cells MH - Humans MH - Insulin/pharmacology MH - Insulin Receptor Substrate Proteins/metabolism MH - Mice MH - Phosphotransferases (Alcohol Group Acceptor)/metabolism MH - Protein Transport PMC - PMC5064357 EDAT- 2016/10/16 06:00 MHDA- 2018/04/12 06:00 PMCR- 2016/10/14 CRDT- 2016/10/15 06:00 PHST- 2016/07/27 00:00 [received] PHST- 2016/09/29 00:00 [accepted] PHST- 2016/10/15 06:00 [entrez] PHST- 2016/10/16 06:00 [pubmed] PHST- 2018/04/12 06:00 [medline] PHST- 2016/10/14 00:00 [pmc-release] AID - srep35438 [pii] AID - 10.1038/srep35438 [doi] PST - epublish SO - Sci Rep. 2016 Oct 14;6:35438. doi: 10.1038/srep35438.