All EMBO Press journals Open Access as of 1 January 2024 - read the FAQs

Research Article
2 December 1996
Free access

Mechanism of activation of protein kinase B by insulin and IGF‐1.

The EMBO Journal
(1996)
15: 6541 - 6551
Insulin activated endogenous protein kinase B alpha (also known as RAC/Akt kinase) activity 12‐fold in L6 myotubes, while after transfection into 293 cells PKBalpha was activated 20‐ and 50‐fold in response to insulin and IGF‐1 respectively. In both cells, the activation of PKBalpha was accompanied by its phosphorylation at Thr308 and Ser473 and, like activation, phosphorylation of both of these residues was prevented by the phosphatidylinositol 3‐kinase inhibitor wortmannin. Thr308 and/or Ser473 were mutated to Ala or Asp and activities of mutant PKBalpha molecules were analysed after transfection into 293 cells. The activity of wild‐type and mutant PKBalpha was also measured in vitro after stoichiometric phosphorylation of Ser473 by MAPKAP kinase‐2. These experiments demonstrated that activation of PKBalpha by insulin or insulin‐like growth factor‐1 (IGF‐1) results from phosphorylation of both Thr308 and Ser473, that phosphorylation of both residues is critical to generate a high level of PKBalpha activity and that the phosphorylation of Thr308 in vivo is not dependent on phosphorylation of Ser473 or vice versa. We propose a model whereby PKBalpha becomes phosphorylated and activated in insulin/IGF‐1‐stimulated cells by an upstream kinase(s).

Formats available

You can view the full content in the following formats:

Information & Authors

Information

Published In

The EMBO Journal cover image
The EMBO Journal
Vol. 15 | No. 23
December 1996
Table of contents
Pages: 6541 - 6551

Article versions

Submission history

Published in issue: December 1996
Published online: 2 December 1996

Permissions

Request permissions for this article.

Authors

Affiliations

D. R. Alessi
MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK.
M. Andjelkovic
MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK.
B. Caudwell
MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK.
P. Cron
MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK.
N. Morrice
MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK.
P. Cohen
MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK.
B. A. Hemmings
MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK.

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Citing Literature

  • PTEN deficiency exposes a requirement for an ARF GTPase module for integrin‐dependent invasion in ovarian cancer, The EMBO Journal, 10.15252/embj.2023113987, 42, 18, (2023).
  • A human kinase yeast array for the identification of kinases modulating phosphorylation‐dependent protein–protein interactions, Molecular Systems Biology, 10.15252/msb.202110820, 18, 3, (2022).
  • Protein abundance of AKT and ERK pathway components governs cell type‐specific regulation of proliferation, Molecular Systems Biology, 10.15252/msb.20167258, 13, 1, (2017).
  • Pten coordinates retinal neurogenesis by regulating Notch signalling, The EMBO Journal, 10.1038/emboj.2011.443, 31, 4, (817-828), (2012).
  • mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide, The EMBO Journal, 10.1038/emboj.2010.271, 29, 23, (3939-3951), (2010).
  • Par‐4 inhibits Akt and suppresses Ras‐induced lung tumorigenesis, The EMBO Journal, 10.1038/emboj.2008.149, 27, 16, (2181-2193), (2008).
  • The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C, The EMBO Journal, 10.1038/emboj.2008.120, 27, 14, (1932-1943), (2008).
  • Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling, The EMBO Journal, 10.1038/emboj.2008.119, 27, 14, (1919-1931), (2008).
  • The pro‐apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1, The EMBO Journal, 10.1038/sj.emboj.7601872, 26, 21, (4523-4534), (2007).
  • Mechanism for activation of the growth factor‐activated AGC kinases by turn motif phosphorylation, The EMBO Journal, 10.1038/sj.emboj.7601682, 26, 9, (2251-2261), (2007).

View Options

View options

PDF

View PDF

Get Access

Media

Figures

Other

Tables

Share

Share

Copy the content Link

Share on social media