Phosphorylation of human eukaryotic initiation factor 2γ: Novel site identification and targeted PKC involvement

Armann Andaya, Weitao Jia, Masaaki Sokabe, Christopher S. Fraser, John W B Hershey, Julie A. Leary

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Eukaryotic translation requires a suite of proteins known as eukaryotic initiation factors (eIFs). These molecular effectors oversee the highly regulated initiation phase of translation. Essential to eukaryotic translation initiation is the protein eIF2, a heterotrimeric protein composed of the individually distinct subunits eIF2α, eIF2β, and eIF2γ. The ternary complex, formed when eIF2 binds to GTP and Met-tRNA i, is responsible for shuttling Met-tRNA i onto the awaiting 40S ribosome. As a necessary component for translation initiation, much attention has been given to the phosphorylation of eIF2α. Despite several previous investigations into eIF2 phosphorylation, most have centered on α- or β-subunit phosphorylation and little is known regarding γ-subunit phosphorylation. Herein, we report eight sites of phosphorylation on the largest eIF2 subunit with seven novel phosphosite identifications via high resolution mass spectrometry. Of the eight sites identified, three are located in either the switch regions or nucleotide binding pocket domain. In addition, we have identified a possible kinase of eIF2, protein kinase C (PKC), which is capable of phosphorylating threonine 66 (thr-66) on the intact heterotrimer. These findings may shed new light on the regulation of ternary complex formation and alternate molecular effectors involved in this process prior to 80S ribosome formation and subsequent translation elongation and termination.

Original languageEnglish (US)
Pages (from-to)4613-4623
Number of pages11
JournalJournal of Proteome Research
Volume10
Issue number10
DOIs
StatePublished - Oct 7 2011

Keywords

  • eukaryotic initiation factor 2
  • mass spectrometry
  • phosphorylation
  • targeted kinase involvement

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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