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First published online October 8, 2008

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Widerborst springs into Akt-ion

Akt (protein kinase B) is a key intermediate in the insulin-IGF signalling (IIS) pathway, and its misregulation is associated with diabetes, obesity and cancer. Recently, several studies have indicated that the activity of Akt (which is upregulated by PI3K and downregulated by PTEN) can be modulated independently in individual subcellular compartments - but what are the mechanisms involved? On page 3383, Clive Wilson and colleagues shed light on this question by identifying Widerborst (Wdb), a regulatory subunit of protein phosphatase 2A (PP2A) in Drosophila, as a key player in the cytoplasm-specific regulation of Akt1. Using a genetic screen for novel phosphatase regulators of IIS, the authors show that Wdb negatively regulates the PI3K-PTEN-Akt signalling cassette, and that it does this by regulating the activity of the PP2A catalytic subunit Microtubule star. In the nurse cells of the ovary, they show, Wdb physically interacts with Akt1 and controls cytoplasmic (but not nuclear) levels of activated Akt1 (pAkt1). In addition, lipid-droplet size is markedly increased in wdb mutants, consistent with the known upregulation of lipid storage by pAkt1. The authors conclude that PP2A regulatory subunits can act as subcellular-compartment-specific regulators of Akt, and might provide new therapeutic targets in insulin-linked disease.

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Related articles in JCS:

The protein phosphatase PP2A-B' subunit Widerborst is a negative regulator of cytoplasmic activated Akt and lipid metabolism in Drosophila

Natalia Vereshchagina, Marie-Christine Ramel, Emmanuelle Bitoun, and Clive Wilson
JCS 2008 121: 3383-3392. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?