| First Author | Mori K | Year | 2005 |
| Journal | Mol Cell Endocrinol | Volume | 230 |
| Issue | 1-2 | Pages | 39-50 |
| PubMed ID | 15664450 | Mgi Jnum | J:149197 |
| Mgi Id | MGI:3847873 | Doi | 10.1016/j.mce.2004.11.004 |
| Citation | Mori K, et al. (2005) Distinct Grb10 domain requirements for effects on glucose uptake and insulin signaling. Mol Cell Endocrinol 230(1-2):39-50 |
| abstractText | The adapter protein Grb10 binds to phosphotyrosine residues in insulin receptors via its C-terminal region and regulates insulin signaling. This study investigated Grb10 regulation of glucose uptake and the importance of the Grb10 N-terminal region using 3T3-L1 adipocytes overexpressing full-length (FL-Grb10) or N-terminally truncated Grb10 (BPS-SH2). Overexpression of FL-Grb10 inhibited insulin-stimulated receptor autophosphorylation and glucose uptake. In contrast, the BPS-SH2 fragment of Grb10 had no effect on receptor phosphorylation or glucose uptake. In spite of these differences, both FL-Grb10 and the BPS-SH2 fragment inhibited insulin-stimulated phosphorylation of IRS1, IRS2, Akt/PKB, Shc, ERK1/2, APS, and c-Cbl to a similar extent. Co-precipitation studies demonstrated more sustained binding of the BPS-SH2 fragment than FL-Grb10 to insulin receptors. Although receptor binding domains of Grb10 are sufficient to inhibit insulin effects on proximal post-receptor signaling responses, N-terminal domains of Grb10 are essential for the effects of this adapter protein on receptor phosphorylation and glucose uptake. |
