Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase‐3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin
- 9 January 1998
- journal article
- Published by Wiley in FEBS Letters
- Vol. 421 (2), 125-130
- https://doi.org/10.1016/s0014-5793(97)01548-2
Abstract
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.Keywords
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