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Regulation of the PI3K pathway by the eIF2α kinase PKR
Author(s) -
Kazemi Shirin,
Baltzis Dionissios,
Su Qiaozhu,
Wang Shuo,
Koromilas Antonis
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a107-c
Subject(s) - protein kinase r , pi3k/akt/mtor pathway , phosphorylation , eif2 , kinase , eif4e , microbiology and biotechnology , phosphoinositide 3 kinase , eukaryotic translation , protein kinase b , signal transduction , protein kinase a , biology , translation (biology) , chemistry , messenger rna , mitogen activated protein kinase kinase , biochemistry , gene
Objective Study the role of PKR in PI3K signaling pathway. Two important steps of translation initiation include the recognition of the mRNA cap structure by eIF4E and the recycling of eIF2. Each step is thought to be regulated independently through the interaction of eIF4E with 4E binding proteins (4E‐BPs) and the phosphorylation of the α subunit of eIF2 at serine 51. Results we demonstrate that the eIF2α kinase PKR provides a link between the two steps. PKR induces phosphoinositide‐3 kinase (PI3K) activity leading to activation of Akt and the mammalian target of Rapamycin (mTOR) and phosphorylation of 4E‐BP1. Despite 4E‐BP1 phosphorylation, its interaction with eIF4E is enhanced in cells with activated PKR and occurs in distinct cytoplasmic granules containing phosphorylated eIF2α. Induction of the PI3K pathway antagonizes the apoptotic effects of PKR caused by eIF2α phosphorylation. PKR is also involved in the activation of PI3K and 4E‐BP1 phosphorylation by serum or interferon (IFN)‐ 1 _. Conclusion Our data demonstrate a novel signaling property of PKR through the regulation of the PI3K pathway. Source of Funding This work has been supported by a grant from the Canadian Institutes of Health Research (CIHR) to Dr. A. Koromilas. S. Kazemi and D. Baltzis are both Research Students of the Terry Fox Foundation through awards from the National Cancer Institute of Canada (NCIC).