Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase‐3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin

FEBS Letters

Loughlin, A.Jane¹  Miller, Christa M¹  Price, Nigel T²  Welsh, Gavin I¹ 

[1] Department of Biosciences, University of Kent at Canterbury, Canterbury CT2 7NJ, UK;Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK

关键词: Eukaryotic initiation factor;    Phosphorylation;    Insulin;    Glycogen synthase kinase-3;   

DOI  :  10.1016/S0014-5793(97)01548-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Eukaryotic initiation factor eIF2B catalyses a key regulatory step in mRNA translation. eIF2B and total protein synthesis are acutely activated by insulin, and this requires phosphatidylinositol 3-kinase (PI 3-kinase). The ϵ-subunit of eIF2B is phosphorylated by glycogen synthase kinase-3 (GSK-3), which is inactivated by insulin in a PI 3-kinase-dependent manner. Here we identify the phosphorylation site in eIF2Bϵ as Ser⁵⁴⁰ and show that treatment of eIF2B with GSK-3 inhibits its activity. Ser⁵⁴⁰ is phosphorylated in intact cells and undergoes dephosphorylation in response to insulin. This is blocked by PI 3-kinase inhibitors. Insulin-induced dephosphorylation of this inhibitory site in eIF2B seems likely to be important in the overall activation of translation by this hormone.

【 授权许可】

Unknown