| First Author | Liu T | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 35438 | PubMed ID | 27739494 |
| Mgi Jnum | J:265618 | Mgi Id | MGI:6201900 |
| Doi | 10.1038/srep35438 | Citation | Liu T, et al. (2016) A novel IRS-1-associated protein, DGKzeta regulates GLUT4 translocation in 3T3-L1 adipocytes. Sci Rep 6:35438 |
| abstractText | 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. |
