| First Author | Kano Y | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 12683 |
| PubMed ID | 31481652 | Mgi Jnum | J:285416 |
| Mgi Id | MGI:6389534 | Doi | 10.1038/s41598-019-48157-6 |
| Citation | Kano Y, et al. (2019) C-SH2 point mutation converts p85beta regulatory subunit of phosphoinositide 3-kinase to an anti-aging gene. Sci Rep 9(1):12683 |
| abstractText | Insulin interacts with the insulin receptor, and the activated receptor promotes activity of the phosphoinositide-3 kinase (PI3K) enzyme. A decrease in insulin or insulin-like growth factor 1 (IGF-1) signaling increases the lifespan in mammalian species. We found that a point mutation in the C-SH2 domain of the p85beta regulatory subunit of PI3K results in a prolonged lifespan. In p85beta mutant cells, nerve growth factor (NGF) activates the longevity protein FOXO, and the mutant p85beta gene produces strong resistance to oxidative stress, which contributes to aging. The p85beta gene mutation causes increased serum insulin and low blood glucose in p85beta mutant transgenic mice. Our results indicate that the p85beta mutant allele alters the activity of downstream targets of PI3K by NGF and platelet-derived growth factor (PDGF) but not by insulin. We report that a point mutation in the C-SH2 domain of p85beta transforms p85beta into a novel anti-aging gene by abnormally regulating PI3K. |
