Altering PI3K-Akt signalling in zebrafish embryos affects PTEN phosphorylation and gastrulation.

BACKGROUND INFORMATION:PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a negative regulator of the PI3K (phosphoinositide 3-kinase)-Akt (also called protein kinase B) signalling pathway and is essential for embryogenesis, but its function in early vertebrate embryos is unclear. RESULTS:To address how PTEN functions in early embryos, we overexpressed one of the four zebrafish PTEN isoforms at the 1-2-cell stage. Overexpression of Ptena454 alters phospho-Akt levels and impairs cell movements associated with gastrulation. Heat shocking embryos increases phospho-Akt levels and lowers phospho-Ptena454 levels. Inhibiting CK2 (protein kinase CK2) activity reduces phospho-Pten levels and augments the effects due to Ptena454 overexpression. Low phospho-Akt and corresponding low phospho-GSK-3 (glycogen synthase kinase-3) and high phospho-Pten levels accompany wortmannin or LY294002 treatment, which inhibit PI3K activity. CONCLUSIONS:These results suggest that Ptena454 regulation is correlated to changes in phospho-Akt levels. We propose a model in which homoeostasis in rapidly dividing and migrating embryonic cells depends on a counterbalance between pro-survival signalling employing CK2 and GSK-3 and the pro-apoptotic activity of Ptena454.

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