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

D. Q. Yang, M. B. Kastan

Research output: Contribution to journalArticle

226 Scopus citations

Abstract

One of the critical responses to insulin treatment is the stimulation of protein synthesis through induced phosphorylation of the elF-4E-binding protein 1 (4E-BP1), and the subsequent release of the translation initiation factor elF-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 rive 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 elF-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.

Original languageEnglish (US)
Pages (from-to)893-898
Number of pages6
JournalNature Cell Biology
Volume2
Issue number12
DOIs
StatePublished - Dec 18 2000
Externally publishedYes

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