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

Biol Cell. 2009 Aug 25;101(11):661-78, 4 p following 678. doi: 10.1042/BC20090034.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Gastrulation*
  • Male
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction*
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*


  • Zebrafish Proteins
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase