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

Eukaryotic initiation factor 2B: identification of multiple phosphorylation sites in the epsilon-subunit and their functions in vivo
Eukaryotic initiation factor 2B: identification of multiple phosphorylation sites in the epsilon-subunit and their functions in vivo
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.
casein kinase, GEF, GSK3, initiation factor, mRNA translation
0261-4189
4349-4359
Wang, X.M.
32ed31f2-84c5-40fd-a703-e2a4d637b492
Paulin, F.E.M.
5e142441-db4d-41d1-ba03-0f6c8c59fe5b
Campbell, L.E.
c7fd39f9-947a-4bc2-af95-3f5b5670b7fd
Gomez, E.
a033b37d-d999-4e2c-a970-4fa9a473641c
Brien, K.
2b9fa9b3-9fbe-4a2a-8c53-ae439e3ee374
Morrice, N.
b8752648-b08e-48d1-99d4-7abb083299e2
Proud, C.G.
c2cc50f9-4565-4d59-9dfc-aa70b9268a6e
Wang, X.M.
32ed31f2-84c5-40fd-a703-e2a4d637b492
Paulin, F.E.M.
5e142441-db4d-41d1-ba03-0f6c8c59fe5b
Campbell, L.E.
c7fd39f9-947a-4bc2-af95-3f5b5670b7fd
Gomez, E.
a033b37d-d999-4e2c-a970-4fa9a473641c
Brien, K.
2b9fa9b3-9fbe-4a2a-8c53-ae439e3ee374
Morrice, N.
b8752648-b08e-48d1-99d4-7abb083299e2
Proud, C.G.
c2cc50f9-4565-4d59-9dfc-aa70b9268a6e

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).

Record type: Article

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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More information

Submitted date: 6 February 2001
Published date: 1 August 2001
Keywords: casein kinase, GEF, GSK3, initiation factor, mRNA translation

Identifiers

Local EPrints ID: 56830
URI: http://eprints.soton.ac.uk/id/eprint/56830
ISSN: 0261-4189
PURE UUID: 3813c497-2d18-44dd-89ba-3e49a2c394a5

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Date deposited: 08 Aug 2008
Last modified: 15 Mar 2024 11:03

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Contributors

Author: X.M. Wang
Author: F.E.M. Paulin
Author: L.E. Campbell
Author: E. Gomez
Author: K. Brien
Author: N. Morrice
Author: C.G. Proud

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