Activation of translation initiation factor eIF2B by insulin requires phosphatidyl inositol 3‐kinase

FEBS Letters

Proud, Christopher G²  Wang, Xuemin²  Kasuga, Masato¹  Stokes, Christa M²  Welsh, Gavin I²  Ogawa, Wataru¹  Sakaue, Hiroshi¹ 

[1] Second Department of Internal Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650, Japan;Department of Biosciences, University of Kent at Canterbury, Canterbury CT2 7NJ, UK

关键词: Initiation factor;    Protein synthesis;    Insulin;    Phosphatidylinositide 3-kinase;    Wortmannin;    Glycogen synthase kinase-3;   

DOI  :  10.1016/S0014-5793(97)00579-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Eukaryotic initiation factor eIF2B mediates a key regulatory step in peptide-chain initiation and is acutely activated by insulin, although it is not clear how. Inhibitors of phosphatidylinositide 3-kinase blocked activation of eIF2B, although rapamycin, which inhibits the p70 S6 kinase pathway, did not. Furthermore, a dominant negative mutant of PI 3-kinase also prevented activation of eIF2B, while a Sos-mutant, which blocks MAP kinase activation, did not. The data demonstrate that a pathway distinct from MAP and p70 S6 kinases regulates eIF2B. Glycogen synthase kinase-3 (GSK-3) phosphorylates and inactivates eIF2B. In all cases, eIF2B and GSK-3 were regulated reciprocally. Dominant negative PI 3-kinase abolished the insulin-induced inhibition of GSK-3. These data strongly support the hypothesis that insulin activates eIF2B through a signalling pathway involving PI 3-kinase and inhibition of GSK-3.

【 授权许可】

Unknown