A novel IRS-1-associated protein, DGK zeta regulates GLUT4 translocation in 3T3-L1 adipocytes

作者：Liu TingYu; Yu BuChin; Kakino Mamoru; Fujimoto Hitoshi; Ando Yasutoshi; Hakuno Fumihiko; Takahashi Shin Ichiro

来源：Scientific Reports, 2016, 6(1): 35438.

DOI：10.1038/srep35438

Insulin receptor substrates (IRSs) are major targets of insulin receptor tyrosine kinases. Here we identified diacylglycerol kinase zeta (DGK zeta) as an IRS-1-associated protein, and examined roles of DGK zeta in glucose transporter 4 (GLUT4) translocation to the plasma membrane. When DGK zeta 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 1 alpha (PIP5K1 alpha), which had been reported to interact with DGK zeta, also inhibited insulin-induced GLUT4 translocation. Moreover, DGK zeta interacted with IRS-1 without insulin stimulation, but insulin stimulation decreased this interaction. Over-expression of sDGK zeta (short-form DGK zeta), which competed out DGK zeta 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 DGK zeta prevents GLUT4 translocation in the absence of insulin and that the DGK zeta dissociated from IRS-1 by insulin stimulation enhances GLUT4 translocation through PIP5K1 alpha activity.

• 出版日期2016-10-14