Abstract

Protein kinase B (PKB) is a proto-oncogene that is activated in signaling pathways initiated by phosphoinositide 3-kinase. Chromatographic separation of brain cytosol revealed a kinase activity that phosphorylated and activated PKB only in the presence of phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P 3 ]. Phosphorylation occurred exclusively on threonine-308, a residue implicated in activation of PKB in vivo. PtdIns(3,4,5)P 3 was determined to have a dual role: Its binding to the pleckstrin homology domain of PKB was required to allow phosphorylation by the upstream kinase and it directly activated the upstream kinase.

Keywords

Pleckstrin homology domainPhosphatidylinositolProtein kinase BPhosphorylationCell biologyKinaseChemistryProtein kinase domainAKT1Proto-Oncogene Proteins c-aktThreonineBiochemistrySignal transductionBiologySerine

Affiliated Institutions

Related Publications

The Phosphoinositide 3-Kinase Pathway

Lewis C. Cantley

Phosphorylated lipids are produced at cellular membranes during signaling events and contribute to the recruitment and activation of various signaling components. The role of ph...

2002 Science 5531 citations

Publication Info

Year
1997
Type
article
Volume
277
Issue
5325
Pages
567-570
Citations
1200
Access
Closed

External Links

View on DOI.org

Social Impact

Altmetric
PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

1200
OpenAlex

Cite This

Terry Copeland, Piers R. J. Gaffney, Colin B. Reese et al. (1997). Dual Role of Phosphatidylinositol-3,4,5-trisphosphate in the Activation of Protein Kinase B. Science , 277 (5325) , 567-570. https://doi.org/10.1126/science.277.5325.567

Identifiers

DOI
10.1126/science.277.5325.567