| First Author | Harrington LS | Year | 2004 |
| Journal | J Cell Biol | Volume | 166 |
| Issue | 2 | Pages | 213-23 |
| PubMed ID | 15249583 | Mgi Jnum | J:91846 |
| Mgi Id | MGI:3050929 | Doi | 10.1083/jcb.200403069 |
| Citation | Harrington LS, et al. (2004) The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol 166(2):213-23 |
| abstractText | Insulin-like growth factors elicit many responses through activation of phosphoinositide 3-OH kinase (PI3K). The tuberous sclerosis complex (TSC1-2) suppresses cell growth by negatively regulating a protein kinase, p70S6K (S6K1), which generally requires PI3K signals for its activation. Here, we show that TSC1-2 is required for insulin signaling to PI3K. TSC1-2 maintains insulin signaling to PI3K by restraining the activity of S6K, which when activated inactivates insulin receptor substrate (IRS) function, via repression of IRS-1 gene expression and via direct phosphorylation of IRS-1. Our results argue that the low malignant potential of tumors arising from TSC1-2 dysfunction may be explained by the failure of TSC mutant cells to activate PI3K and its downstream effectors. |
