| First Author | Sheen MR | Year | 2015 |
| Journal | Open Life Sci | Volume | 10 |
| Issue | 1 | Pages | 461-478 |
| PubMed ID | 27482546 | Mgi Jnum | J:251785 |
| Mgi Id | MGI:6102178 | Doi | 10.1515/biol-2015-0048 |
| Citation | Sheen MR, et al. (2015) Myristoylated p110alpha Causes Embryonic Death Due to Developmental and Vascular Defects. Open Life Sci 10(1):461-478 |
| abstractText | The phosphatidylinositol 3-kinase (PI3K) signaling pathway regulates many important cellular functions. The functional impact of deregulating the PIK3CA gene, encoding the p110alpha catalytic subunit of PI3K, is validated by frequent gain of function mutations in a range of human cancers. We generated a mouse model with an inducible constitutively active form of PI3K. In this model Cre recombinase activates expression of a myristoylated form of p110alpha (myr-p110alpha). The myristoylated version of p110alpha brings the protein to the cytoplasmic side of the cell membrane, which mimics the normal activation mechanism for the p110alpha catalytic subunit and activates the PI3K enzyme. Constitutively activated PI3K signaling induced by myr-p110alpha in all cells of the developing mouse caused lethality during embryonic development. Transgenic Cre;myr-p110alpha heterozygous embryos displayed morphological malformation and poor vascular development with extremely dilated blood vessels and hemorrhage in the embryo and the extraembryonic yolk sac. Previous studies demonstrated that loss of p110alpha during embryonic development causes angiogenic disruption and here we show that constitutive activation of p110alpha by gain of function mutation during development also disrupts vasculogenesis/angiogenesis in what appears to be a similar manner. These finding demonstrate the importance of tight regulation of PI3K signaling during embryonic vasculogenesis/angiogenesis.. |
