| First Author | Takeuchi M | Year | 2012 |
| Journal | Biochim Biophys Acta | Volume | 1823 |
| Issue | 12 | Pages | 2210-6 |
| PubMed ID | 22974639 | Mgi Jnum | J:193212 |
| Mgi Id | MGI:5467903 | Doi | 10.1016/j.bbamcr.2012.08.019 |
| Citation | Takeuchi M, et al. (2012) Diacylglycerol kinase delta1 transiently translocates to the plasma membrane in response to high glucose. Biochim Biophys Acta 1823(12):2210-6 |
| abstractText | The type II diacylglycerol kinases (DGKs) contain several functional domains such as a pleckstrin homology (PH) domain, two C1 domains and a sterile alpha-motif (SAM) domain. It was previously revealed that DGKdelta contributes to hyperglycemia-induced peripheral insulin resistance and thereby exacerbate the severity of type 2 diabetes. Moreover, a high extracellular concentration of glucose activated DGKdelta in skeletal muscle cells, which was followed by a reduction in the intracellular diacylglycerol levels and the inactivation of protein kinase Calpha, the enzyme that phosphorylates and inactivates the insulin receptor. However, the intracellular behavior of DGKdelta upon high glucose stimulation remains unclear. In this study, we found that DGKdelta1, but not a splice variant DGKdelta2 or the other type II DGKeta1/2, translocated from the cytoplasm to the plasma membrane in human embryonic kidney HEK293 and mouse myoblast C2C12 cells within 5 min in response to high glucose levels. The translocation was inhibited by phosphatidylinositol 3-kinase inhibitors, LY294002 and GDC-0941, suggesting that the event is regulated via the phosphatidylinositol 3-kinase pathway. Moreover, we revealed that the PH and C1 domains are responsible for the plasma membrane translocation and that the SAM domain negatively regulates the translocation. These results indicate that DGKdelta1 is the sole type II DGK isoform that responds rapidly and dynamically to high glucose levels. |
