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

Wang, X.M., Paulin, F.E.M., Campbell, L.E., Gomez, E., Brien, K., Morrice, N. and Proud, C.G. (2001) Eukaryotic initiation factor 2B: identification of multiple phosphorylation sites in the epsilon-subunit and their functions in vivo. The EMBO Journal, 20 (16), 4349-4359. (doi:10.1093/emboj/20.16.4349).

Abstract

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 (e) 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 eIF2Be 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 eIF2Be in vivo. The ®fth site, which lies outside the catalytic domain of eIF2Be, can be phosphorylated by casein kinase 1. All ®ve sites are phosphorylated in the eIF2B complex in vivo.

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