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Nat Cell Biol. 2000 Dec;2(12):893-8.

Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1.

Author information

1
Department of Hematology-Oncology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105-2794, USA.

Abstract

One of the critical responses to insulin treatment is the stimulation of protein synthesis through induced phosphorylation of the eIF-4E-binding protein 1 (4E-BP1), and the subsequent release of the translation initiation factor, eIF-4E. Here we report that ATM, the protein product of the ATM gene that is mutated in the disease ataxia telangiectasia, phosphorylates 4E-BP1 at Ser 111 in vitro and that insulin treatment induces phosphorylation of 4E-BP1 at Ser 111 in vivo in an ATM-dependent manner. In addition, insulin treatment of cells enhances the specific kinase activity of ATM. Cells lacking ATM kinase activity exhibit a significant decrease in the insulin-induced dissociation of 4E-BP1 from eIF-4E. These results suggest an unexpected role for ATM in an insulin-signalling pathway that controls translation initiation. Through this mechanism, a lack of ATM activity probably contributes to some of the metabolic abnormalities, such as poor growth and insulin resistance, reported in ataxia telangiectasia cells and patients with ataxia telangiectasia.

PMID:
11146653
DOI:
10.1038/35046542
[Indexed for MEDLINE]

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