Finkielsztein, A., and Kelly, G.M. (2009) Altering PI3K—Akt signalling in zebrafish embryos affects PTEN phosphorylation and gastrulation. Biology of the cell. 101(11):661–682.
Background information. PTEN is a negative regulator of the PI3K-Akt signaling pathway and 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 endogenous phospho-Ptena454 levels. Inhibiting protein kinase CK2 activity also reduces phospho-Ptena454 levels and augments the effects due to Ptena454 overexpression. Low phospho-Akt and corresponding low phospho-Gsk-3 and high phospho-Ptena454 levels accompany wortmannin or LY294002 treatment, which inhibit PI3K activity. Conclusions. These data suggest that Ptena454 regulation is correlated to changes in phospho-Akt levels. We propose a model by which homeostasis in rapidly dividing and migrating embryonic cells depends on a counterbalance between pro-survival signaling employing CK2 and Gsk-3 and the pro-apoptotic activity of Ptena454.