Publication Date:
1997-07-25
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokoe, D -- Stephens, L R -- Copeland, T -- Gaffney, P R -- Reese, C B -- Painter, G F -- Holmes, A B -- McCormick, F -- Hawkins, P T -- New York, N.Y. -- Science. 1997 Jul 25;277(5325):567-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA. stokoe@cc.ucsf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9228007" target="_blank"〉PubMed〈/a〉
Keywords:
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/*metabolism
;
Proto-Oncogene Proteins/chemistry/*metabolism
;
Proto-Oncogene Proteins c-akt
;
Rats
;
Rats, Sprague-Dawley
;
Signal Transduction
;
Stereoisomerism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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