Identification of interprotein interactions between the subunits of eukaryotic initiation factors eIF2 and eIF2B

Scot R. Kimball, Nina K. Heinzinger, Rick L. Horetsky, Leonard S. Jefferson

    Research output: Contribution to journalArticlepeer-review

    44 Scopus citations

    Abstract

    Modulation of protein/protein interaction is an important mechanism involved in regulation of translation initiation. Specifically, regulation of the interaction of elF2 with the guanine nucleotide exchange factor, eIF2B, is a key mechanism for controlling translation under a variety of conditions. Phosphorylation of the α-subunit of eIF2 converts the protein into a competitive inhibitor of eIF2B by causing an increase in the binding affinity of eIF2B for eIF2. Consequently, it has been assumed that the α-subunit of eIF2 is directly involved in binding to eIF2B. In the present study, eIF2 was found to bind only to the σ- and ε-subunits of eIF2B, and eIF2B was shown to bind only to the β-subunit of eIF2 by far-Western blot analysis. The binding site on eIF2β for either the eIF2B holoprotein, or the isolated σ- or ε-subunits of eIF2B was shown to be located within approximately 70 amino acids of the C terminus of the protein. Phosphorylation of the α-subunit of eIF2 did not promote binding of eIF2B to the isolated subunit. However, it did cause an increase in the affinity of eIF2B for eIF2. Finally, phosphorylation by protein kinase A of the β-subunit of eIF2 in the C- terminal portion of the protein increased the guanine nucleotide exchange activity of eIF2B, whereas phosphorylation by casein kinase II or protein kinase C was without effect.

    Original languageEnglish (US)
    Pages (from-to)3039-3044
    Number of pages6
    JournalJournal of Biological Chemistry
    Volume273
    Issue number5
    DOIs
    StatePublished - Jan 30 1998

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Fingerprint

    Dive into the research topics of 'Identification of interprotein interactions between the subunits of eukaryotic initiation factors eIF2 and eIF2B'. Together they form a unique fingerprint.

    Cite this