Eukaryotic initiation factor 2B:: identification of multiple phosphorylation sites in the ε-subunit and their functions in vivo

被引:99
作者
Wang, XM
Paulin, FEM
Campbell, LE
Gomez, E
O'Brien, K
Morrice, N
Proud, CG
机构
[1] Univ Dundee, Div Mol Physiol, Sch Life Sci, Dundee DD1 5EH, Scotland
[2] Univ Dundee, MRC, Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland
关键词
casein kinase; GEF; GSK3; initiation factor; mRNA translation;
D O I
10.1093/emboj/20.16.4349
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (epsilon) 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 eIF2B epsilon 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 eIF2B epsilon in vivo. The fifth site, which lies outside the catalytic domain of eIF2B epsilon, can be phosphorylated by casein kinase 1. All five sites are phosphorylated in the eIF2B complex in vivo.
引用
收藏
页码:4349 / 4359
页数:11
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