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Living with lethal PIP3 levels: viability of flies lacking PTEN restored by a PH domain mutation in Akt/PKB.


Stocker, H; Andjelkovic, M; Oldham, S; Laffargue, M; Wymann, M P; Hemmings, B A; Hafen, E (2002). Living with lethal PIP3 levels: viability of flies lacking PTEN restored by a PH domain mutation in Akt/PKB. Science, 295(5562):2088-2091.

Abstract

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.

Abstract

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.

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133 citations in Web of Science®
139 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:07 Faculty of Science > Institute of Zoology (former)
Dewey Decimal Classification:570 Life sciences; biology
590 Animals (Zoology)
Language:English
Date:15 March 2002
Deposited On:11 Feb 2008 12:17
Last Modified:05 Apr 2016 12:15
Publisher:American Association for the Advancement of Science (AAAS)
ISSN:0036-8075
Publisher DOI:https://doi.org/10.1126/science. 1068094
PubMed ID:11872800

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