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Eukaryotic initiation factor 2B: identification of multiple phosphorylation sites in the ϵ‐subunit and their functions in vivo
Author(s) -
Wang Xuemin,
Paulin Fiona E.M.,
Campbell Linda E.,
Gomez Edith,
O'Brien Kirsty,
Morrice Nicholas,
Proud Christopher G.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.16.4349
Subject(s) - biology , phosphorylation , casein kinase 1 , casein kinase 2 , gsk 3 , protein subunit , guanine nucleotide exchange factor , microbiology and biotechnology , eif2 , biochemistry , kinase , eukaryotic initiation factor , phosphorylation cascade , protein kinase a , protein phosphorylation , translation (biology) , signal transduction , mitogen activated protein kinase kinase , messenger rna , gene
Eukaryotic initiation factor (eIF) 2B is a heteromeric guanine nucleotide exchange factor that plays an important role in regulating mRNA translation. Here we identify multiple phosphorylation sites in the largest, catalytic, subunit (ϵ) of mammalian eIF2B. These sites are phosphorylated by four different protein kinases. Two conserved sites (Ser712/713) are phosphorylated by casein kinase 2. They lie at the extreme C‐terminus and are required for the interaction of eIF2Bϵ with its substrate, eIF2, in vivo and for eIF2B activity in vitro . Glycogen synthase kinase 3 (GSK3) is responsible for phosphorylating Ser535. This regulatory phosphorylation event requires both the fourth site (Ser539) and a distal region, which acts to recruit GSK3 to eIF2Bϵ in vivo . The fifth site, which lies outside the catalytic domain of eIF2Bϵ, can be phosphorylated by casein kinase 1. All five sites are phosphorylated in the eIF2B complex in vivo .