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Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase‐3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin
Author(s) -
Welsh Gavin I,
Miller Christa M,
Loughlin A.Jane,
Price Nigel T
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01548-2
Subject(s) - gsk 3 , glycogen synthase , dephosphorylation , biology , eif2 , biochemistry , phosphorylation , microbiology and biotechnology , chemistry , translation (biology) , phosphatase , messenger rna , gene
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 Ser 540 and show that treatment of eIF2B with GSK‐3 inhibits its activity. Ser 540 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.