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Inappropriate regulation of the PI3-kinase/PTEN/Akt kinase-signalling cassette, a key downstream target of insulin/insulin-like growth factor signalling (IIS), is associated with several major human diseases such as diabetes, obesity and cancer. In Drosophila, studies have recently revealed that different subcellular pools of activated, phosphorylated Akt can modulate different IIS-dependent processes. For example, a specific pool of activated Akt within the cytoplasm alters aspects of lipid metabolism, a process that is misregulated in both obesity and diabetes. However, it remains unclear how this pool is regulated. Here we show that the protein phosphatase PP2A-B' regulatory subunit Widerborst (Wdb), which coimmunoprecipitates with Akt in vivo, selectively modulates levels of activated Akt in the cytoplasm. It alters lipid droplet size and expression of the lipid storage perilipin-like protein LSD2 in the Drosophila ovary, but not in epithelial cells of the eye imaginal discs. We conclude that isoforms of PP2A-B' can act as subcellular-compartment-specific regulators of PI3-kinase/PTEN/Akt kinase signalling and IIS, potentially providing new targets for modulating individual subcellular pools of activated Akt in insulin-linked disease.

Original publication

DOI

10.1242/jcs.035220

Type

Journal article

Journal

J Cell Sci

Publication Date

15/10/2008

Volume

121

Pages

3383 - 3392

Keywords

Animals, Cytoplasm, Diabetes Mellitus, Drosophila Proteins, Drosophila melanogaster, Enzyme Activation, Humans, Insulin, Lipid Metabolism, Neoplasms, Obesity, Organ Specificity, PTEN Phosphohydrolase, Phosphatidylinositol 3-Kinases, Phosphorylation, Protein Phosphatase 2, Proto-Oncogene Proteins c-akt