Involvement of the p110 alpha isoform of PI3K in early development of mouse embryos

Mol Reprod Dev. 2009 Apr;76(4):389-98. doi: 10.1002/mrd.20978.

Abstract

Class I of phosphoinositide 3-kinases (PI3Ks) is characterized as a group of intracellular signal proteins possessing both protein and lipid kinase activities. Recent studies implicate class I of PI3Ks acts as indispensable mediators in early development of mouse embryos, but the molecular mechanisms are poorly defined. In this paper, mouse one-cell embryos were used to investigate a possible contribution of the catalytic subunit of PI3K, p110 alpha, to cell cycle progression. The expression level of p110 alpha was determined in four phases of one-cell embryos. Silencing of p110 alpha by microinjection of p110 alpha shRNA into one-cell embryos resulted in a G2/M arrest and prevented the activation of Akt and M-phase promoting factor (MPF). Further, microinjection of the synthesized mRNA coding for a constitutively active p110 alpha into one-cell embryos induced cell cleavage more effectively than microinjection of wild-type p110 alpha mRNA, whereas microinjection of mRNA of kinase-deficient p110 alpha delayed the first mitotic cleavage. Taken together, this study demonstrates that p110 alpha is significant for G2/M transition of mouse one-cell embryos and further emphasizes the importance of Akt in PI3K pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / physiology
  • Class I Phosphatidylinositol 3-Kinases
  • Embryo, Mammalian* / enzymology
  • Embryo, Mammalian* / physiology
  • Female
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Mesothelin
  • Mice
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Pregnancy
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference

Substances

  • Isoenzymes
  • Msln protein, mouse
  • 1-phosphatidylinositol 3-kinase p110 subunit, mouse
  • Class I Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Mesothelin