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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
3-Phosphoinositide-Dependent Protein Kinases
-
Adenosine Triphosphate / metabolism
-
Amino Acid Sequence
-
Animals
-
Blood Proteins / chemistry
-
Brain / enzymology
-
COS Cells
-
Cytosol / enzymology
-
Enzyme Activation
-
Humans
-
Male
-
Molecular Sequence Data
-
Phosphatidylinositol Phosphates / metabolism*
-
Phosphoproteins*
-
Phosphorylation
-
Phosphothreonine / metabolism
-
Protein Serine-Threonine Kinases / chemistry
-
Protein Serine-Threonine Kinases / metabolism*
-
Proto-Oncogene Mas
-
Proto-Oncogene Proteins / chemistry
-
Proto-Oncogene Proteins / metabolism*
-
Proto-Oncogene Proteins c-akt
-
Rats
-
Rats, Sprague-Dawley
-
Signal Transduction
-
Stereoisomerism
Substances
-
Blood Proteins
-
MAS1 protein, human
-
Phosphatidylinositol Phosphates
-
Phosphoproteins
-
Proto-Oncogene Mas
-
Proto-Oncogene Proteins
-
phosphatidylinositol 3,4,5-triphosphate
-
platelet protein P47
-
Phosphothreonine
-
Adenosine Triphosphate
-
3-Phosphoinositide-Dependent Protein Kinases
-
Protein Serine-Threonine Kinases
-
Proto-Oncogene Proteins c-akt