Publication Date:
2002-03-02
Description:
The phosphoinositide phosphatase PTEN is mutated in many human cancers. Although the role of PTEN has been studied extensively, the relative contributions of its numerous potential downstream effectors to deregulated growth and tumorigenesis remain uncertain. We provide genetic evidence in Drosophila melanogaster for the paramount importance of the protein kinase Akt [also called protein kinase B (PKB)] in mediating the effects of increased phosphatidylinositol 3,4,5-trisphosphate (PIP3) concentrations that are caused by the loss of PTEN function. A mutation in the pleckstrin homology (PH) domain of Akt that reduces its affinity for PIP3 sufficed to rescue the lethality of flies devoid of PTEN activity. Thus, Akt appears to be the only critical target activated by increased PIP3 concentrations in Drosophila.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stocker, Hugo -- Andjelkovic, Mirjana -- Oldham, Sean -- Laffargue, Muriel -- Wymann, Matthias P -- Hemmings, Brian A -- Hafen, Ernst -- New York, N.Y. -- Science. 2002 Mar 15;295(5562):2088-91. Epub 2002 Feb 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Zoologisches Institut der Universitat Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11872800" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
Amino Acid Substitution
;
Animals
;
Cell Line
;
Cell Membrane/enzymology
;
Drosophila Proteins/chemistry/genetics/metabolism
;
Drosophila melanogaster/genetics/*physiology
;
Eye/growth & development
;
Female
;
Genes, Insect
;
Humans
;
Insulin/pharmacology
;
Male
;
Mutation
;
PTEN Phosphohydrolase
;
Phenotype
;
Phosphatidylinositol 4,5-Diphosphate/metabolism
;
Phosphatidylinositol Phosphates/*metabolism
;
Phosphoric Monoester Hydrolases/*genetics/*physiology
;
Photoreceptor Cells, Invertebrate/growth & development
;
Protein Structure, Tertiary
;
Protein-Serine-Threonine Kinases/chemistry/*genetics/metabolism
;
Proto-Oncogene Proteins/chemistry/*genetics/metabolism
;
Proto-Oncogene Proteins c-akt
;
Transfection
;
Tumor Suppressor Proteins/*genetics/*physiology
;
Vanadates/pharmacology
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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