Role of the phosphoinositide 3-kinase pathway in mouse embryonic stem (ES) cells

Biochem Soc Trans. 2005 Dec;33(Pt 6):1522-5. doi: 10.1042/BST0331522.

Abstract

Mouse ES (embryonic stem) cells maintain pluripotency with robust proliferation in vitro. ES cells share some similarities with cancer cells, such as anchorage-independent growth, loss of contact inhibition and tumour formation. After differentiation, ES cells lose pluripotency and tumorigenicity. Recent studies showed that the PI3K (phosphoinositide 3-kinase) pathway is important for proliferation, survival and maintenance of pluripotency in ES cells. The PI3K pathway is activated by growth factors and cytokines including insulin and leukaemia inhibitory factor. In addition to these exogenous factors, the PI3K pathway is endogenously activated by the constitutively active Ras family protein ERas (ES cell-expressed Ras). The PI3K pathway utilizes multiple downstream effectors including mTOR (mammalian target of rapamycin), which we have shown to be essential for proliferation in mouse ES cells and early embryos.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Embryo, Mammalian / anatomy & histology
  • Embryo, Mammalian / physiology
  • Mice
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Oncogene Protein p21(ras) / genetics
  • Oncogene Protein p21(ras) / metabolism
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein Kinases / metabolism
  • Signal Transduction / physiology*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • TOR Serine-Threonine Kinases

Substances

  • ERas protein, mouse
  • Protein Kinases
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • Pten protein, mouse
  • Oncogene Protein p21(ras)