T-cell activation leads to rapid stimulation of translation initiation factor eIF2B and inactivation of glycogen synthase kinase-3

Gavin I. Welsh, Suzanne Miyamoto, Nigel T. Priced, Brian Safer, Christopher G. Proud

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Mitogenic stimulation of T-lymphocytes causes a rapid activation of protein synthesis, which reflects in part increased expression of many translation components. Their levels, however, rise more slowly than the rate of protein synthesis, indicating an enhancement of the efficiency of their utilization. Initiation factor eIF2B catalyzes a key regulatory step in the initiation of translation, and we have therefore studied its activity following T-cell activation. eIF2B activity rises quickly, increasing as early as 5 min after cell stimulation. This initial phase is followed by an additional slow but substantial increase in eIF2B activity. The level of eIF2B subunits did not change over the initial rapid phase but did increase at later time points. Northern analysis revealed that levels of eIF2B mRNA only rose during the later phase. The rapid activation of eIF2B following mitogenic stimulation of T-cells is therefore mediated by factors other than its own concentration. The largest (ε) subunit of eIF2B is a substrate for glycogen synthase kinase-3 (GSK-3), the activity of which rapidly decreases following T-cell activation. Since phosphorylation of eIF2B by GSK-3 appears to inhibit nucleotide exchange in vitro, this provides a potential mechanism by which eIF2B may be activated.

Original languageEnglish (US)
Pages (from-to)11410-11413
Number of pages4
JournalJournal of Biological Chemistry
Volume271
Issue number19
DOIs
StatePublished - 1996
Externally publishedYes

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Glycogen Synthase Kinase 3
Peptide Initiation Factors
T-cells
Chemical activation
T-Lymphocytes
Phosphorylation
Proteins
Nucleotides
Messenger RNA
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

T-cell activation leads to rapid stimulation of translation initiation factor eIF2B and inactivation of glycogen synthase kinase-3. / Welsh, Gavin I.; Miyamoto, Suzanne; Priced, Nigel T.; Safer, Brian; Proud, Christopher G.

In: Journal of Biological Chemistry, Vol. 271, No. 19, 1996, p. 11410-11413.

Research output: Contribution to journalArticle

Welsh, Gavin I. ; Miyamoto, Suzanne ; Priced, Nigel T. ; Safer, Brian ; Proud, Christopher G. / T-cell activation leads to rapid stimulation of translation initiation factor eIF2B and inactivation of glycogen synthase kinase-3. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 19. pp. 11410-11413.
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AU - Proud, Christopher G.

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