Altering PI3K-Akt signalling in zebrafish embryos affects PTEN phosphorylation and gastrulation.
BACKGROUND
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.
Finkielsztein
Ariel
A
Department of Biology, Molecular Genetics Unit, University of Western Ontario, London, ON, Canada.
Kelly
Gregory M
GM
D000818:Animals; D005260:Female; D054262:Gastrulation; D008297:Male; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D029961:Zebrafish Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase