Title | Adenovirus Protein E4-ORF1 Activation of PI3 Kinase Reveals Differential Regulation of Downstream Effector Pathways in Adipocytes. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Chaudhary N, Gonzalez E, Chang S-H, Geng F, Rafii S, Altorki NK, McGraw TE |
Journal | Cell Rep |
Volume | 17 |
Issue | 12 |
Pagination | 3305-3318 |
Date Published | 2016 Dec 20 |
ISSN | 2211-1247 |
Keywords | Adenovirus E4 Proteins, Adipocytes, Animals, Cell Membrane, Forkhead Box Protein O1, Gene Expression Regulation, Glucose Transporter Type 1, Glucose Transporter Type 4, Humans, Insulin, Mice, Phosphatidylinositol 3-Kinases, rab GTP-Binding Proteins, Signal Transduction, Transfection |
Abstract | <p>Insulin activation of phosphatidylinositol 3-kinase (PI3K) regulates metabolism, including the translocation of the Glut4 glucose transporter to the plasma membrane and inactivation of the FoxO1 transcription factor. Adenoviral protein E4-ORF1 stimulates cellular glucose metabolism by mimicking growth-factor activation of PI3K. We have used E4-ORF1 as a tool to dissect PI3K-mediated signaling in adipocytes. E4-ORF1 activation of PI3K in adipocytes recapitulates insulin regulation of FoxO1 but not regulation of Glut4. This uncoupling of PI3K effects occurs despite E4-ORF1 activating PI3K and downstream signaling to levels achieved by insulin. Although E4-ORF1 does not fully recapitulate insulin's effects on Glut4, it enhances insulin-stimulated insertion of Glut4-containing vesicles to the plasma membrane independent of Rab10, a key regulator of Glut4 trafficking. E4-ORF1 also stimulates plasma membrane translocation of ubiquitously expressed Glut1 glucose transporter, an effect that is likely essential for E4-ORF1 to promote an anabolic metabolism in a broad range of cell types.</p> |
DOI | 10.1016/j.celrep.2016.11.082 |
Alternate Journal | Cell Rep |
PubMed ID | 28009298 |
PubMed Central ID | PMC5193245 |
Grant List | R01 DK052852 / DK / NIDDK NIH HHS / United States R01 DK096925 / DK / NIDDK NIH HHS / United States R56 DK052852 / DK / NIDDK NIH HHS / United States R56 DK096925 / DK / NIDDK NIH HHS / United States |