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

Publication ,  Journal Article
Yang, DQ; Kastan, MB
Published in: Nat Cell Biol
December 2000

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.

Duke Scholars

Published In

Nat Cell Biol

DOI

ISSN

1465-7392

Publication Date

December 2000

Volume

2

Issue

12

Start / End Page

893 / 898

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Transfection
  • Signal Transduction
  • Serine
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Phosphoproteins
  • Peptide Initiation Factors
  • Models, Biological
  • Mice
 

Citation

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MLA
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Yang, D. Q., & Kastan, M. B. (2000). Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1. Nat Cell Biol, 2(12), 893–898. https://doi.org/10.1038/35046542
Yang, D. Q., and M. B. Kastan. “Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1.Nat Cell Biol 2, no. 12 (December 2000): 893–98. https://doi.org/10.1038/35046542.
Yang, D. Q., and M. B. Kastan. “Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1.Nat Cell Biol, vol. 2, no. 12, Dec. 2000, pp. 893–98. Pubmed, doi:10.1038/35046542.

Published In

Nat Cell Biol

DOI

ISSN

1465-7392

Publication Date

December 2000

Volume

2

Issue

12

Start / End Page

893 / 898

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Transfection
  • Signal Transduction
  • Serine
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Phosphoproteins
  • Peptide Initiation Factors
  • Models, Biological
  • Mice