Publication Date:
1997-01-31
Description:
The regulation of the serine-threonine kinase Akt by lipid products of phosphoinositide 3-kinase (PI 3-kinase) was investigated. Akt activity was found to correlate with the amount of phosphatidylinositol-3,4-bisphosphate (PtdIns-3,4-P2) in vivo, and synthetic PtdIns-3,4-P2 activated Akt both in vitro and in vivo. Binding of PtdIns-3,4-P2 occurred within the Akt pleckstrin homology (PH) domain and facilitated dimerization of Akt. Akt mutated in the PH domain was not activated by PI 3-kinase in vivo or by PtdIns-3, 4-P2 in vitro, and it was impaired in binding to PtdIns-3,4-P2. Examination of the binding to other phosphoinositides revealed that they bound to the Akt PH domain with much lower affinity than did PtdIns-3,4-P2 and failed to increase Akt activity. Thus, Akt is apparently regulated by the direct interaction of PtdIns-3,4-P2 with the Akt PH domain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Franke, T F -- Kaplan, D R -- Cantley, L C -- Toker, A -- GM41890/GM/NIGMS NIH HHS/ -- N01-CO-74101/CO/NCI NIH HHS/ -- R01 GM041890/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1997 Jan 31;275(5300):665-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research Facility and Development Center (NCI-FCRFDC), Frederick, MD 21702, USA. tfranke@bidmc.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9005852" target="_blank"〉PubMed〈/a〉
Keywords:
3T3 Cells
;
Animals
;
COS Cells
;
Dimerization
;
Enzyme Activation
;
Mice
;
Phosphatidylinositol 3-Kinases
;
Phosphatidylinositol Phosphates/*metabolism/pharmacology
;
Phosphorylation
;
Phosphotransferases (Alcohol Group Acceptor)/metabolism
;
Platelet-Derived Growth Factor/pharmacology
;
Point Mutation
;
Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism
;
Proto-Oncogene Proteins/chemistry/genetics/*metabolism
;
Proto-Oncogene Proteins c-akt
;
Recombinant Fusion Proteins/chemistry/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
