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PMID:17918740
| Citation |
Sephton, CF and Mousseau, DD (2008) Dephosphorylation of Akt in C6 cells grown in serum-free conditions corresponds with redistribution of p85/PI3K to the nucleus. J. Neurosci. Res. 86:675-82 |
|---|---|
| Abstract |
Withdrawal of serum from cell cultures constitutes a useful model for the study of mechanisms involved in the regulation of Akt function in vitro. However, there have been several reports of changes in Akt activity that are not fully explained by the current model of phosphatidylinositol 3'-kinase (PI3K)/Akt signaling. We demonstrate the expected loss of Akt phosphorylation in C6 glioma cells cultured in serum-free conditions, yet we also observed a paradoxical increase in PI3K-lipid kinase activity in the same cultures. These events corresponded with relocalization of p85, the regulatory subunit of PI3K, to the perinuclear region and a local increase in PI3K-lipid kinase products. Treatment with platelet-derived growth factor (PDGF) maintained the association between p85 and the PDGF receptor during serum withdrawal and restored PI3K-lipid production at the plasma membrane. Although this protected Akt from dephosphorylation, it only slightly reversed cell-cycle arrest. These effects were not sensitive to treatment with epidermal growth factor, thus precluding a generalized role for growth factors. Our data suggest that loss of growth factor signaling, including PDGF signaling, may disrupt recruitment and/or anchoring of an active p85(PI3K) complex at the plasma membrane during serum withdrawal, which could account for the concurrent loss of Akt function. |
| Links |
PubMed Online version:10.1002/jnr.21516 |
| Keywords |
Animals; Cell Cycle/drug effects; Cell Line, Tumor; Cell Membrane/metabolism; Cell Nucleus/enzymology; Cell Proliferation/drug effects; Culture Media, Serum-Free/pharmacology; Glioma/metabolism; Glioma/pathology; Lipid Metabolism; Phosphatidylinositol 3-Kinases/biosynthesis; Phosphatidylinositol 3-Kinases/metabolism; Phosphatidylinositol Phosphates/biosynthesis; Phosphorylation/drug effects; Phosphotransferases/metabolism; Platelet-Derived Growth Factor/pharmacology; Proto-Oncogene Proteins c-akt/metabolism; Rats; Tissue Distribution/drug effects |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
part_of |
GO:0005634: nucleus |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
Notes
See also
References
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