Gain of function by phosphorylation in Presenilin 1-mediated regulation of insulin signaling (pages 964–973)
Masato Maesako, Kengo Uemura, Akira Kuzuya, Kazuki Sasaki, Megumi Asada, Kiwamu Watanabe, Koichi Ando, Masakazu Kubota, Haruhiko Akiyama, Ryosuke Takahashi, Takeshi Kihara, Shun Shimohama and Ayae Kinoshita
Version of Record online: 23 APR 2012 | DOI: 10.1111/j.1471-4159.2012.07741.x
The function of phosphorylated Presenilin 1 has not been elucidated. We demonstrate that phosphorylated Presenilin 1 at the serine 353 and 357 residues down-regulated the expression of insulin receptor compared with wild-type Presenilin 1, thus suggesting that phosphorylated PS1 may play the crucial role in a positive feed-forward cycle inhibiting insulin signaling. From our findings, insulin signaling dysfunction may be associated with the pathogenesis of Alzheimer disease.