Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B.
basic_science · Level V
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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)P3]. Phosphorylation occurred exclusively on threonine-308, a residue implicated in activation of PKB in vivo. PtdIns(3,4,5)P3 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.
Medical subject headings
- Phosphatidylinositol Phosphates
- Phosphoproteins
- Protein Serine-Threonine Kinases
- Proto-Oncogene Proteins