Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1.
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.
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Related Subject Headings
- Tumor Suppressor Proteins
- Transfection
- Signal Transduction
- Serine
- Protein Serine-Threonine Kinases
- Phosphorylation
- Phosphoproteins
- Peptide Initiation Factors
- Models, Biological
- Mice
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Suppressor Proteins
- Transfection
- Signal Transduction
- Serine
- Protein Serine-Threonine Kinases
- Phosphorylation
- Phosphoproteins
- Peptide Initiation Factors
- Models, Biological
- Mice