Binding of Ras to phosphoinositide 3-kinase p110? is required for Ras- driven tumorigenesis in mice

Gupta, Surbhi, Ramjaun, Antoine R., Haiko, Paula, Wang, Yihua, Warne, Patricia H., Nicke, Barbara, Nye, Emma, Stamp, Gordon, Alitalo, Kari and Downward, Julian (2007) Binding of Ras to phosphoinositide 3-kinase p110? is required for Ras- driven tumorigenesis in mice. Cell, 129 (5), 957-968. (doi:10.1016/j.cell.2007.03.051). (PMID:17540175)

Abstract

Ras proteins signal through direct interaction with a number of effector enzymes, including type I phosphoinositide (PI) 3-kinases. Although the ability of Ras to control PI 3-kinase has been well established in manipulated cell culture models, evidence for a role of the interaction of endogenous Ras with PI 3-kinase in normal and malignant cell growth in vivo has been lacking. Here we generate mice with mutations in the Pi3kca gene encoding the catalytic p110? isoform that block its interaction with Ras. Cells from these mice show proliferative defects and selective disruption of signaling from growth factors to PI 3-kinase. The mice display defective development of the lymphatic vasculature, resulting in perinatal appearance of chylous ascites. Most importantly, they are highly resistant to endogenous Ras oncogene-induced tumorigenesis. The interaction of Ras with p110? is thus required in vivo for certain normal growth factor signaling and for Ras-driven tumor formation.

This record has no associated files available for download.

Contributors

Author: Yihua Wang

Download statistics