PHOSPHATIDYLINOSITOL-3-OH KINASE AS A DIRECT TARGET OF RAS

Ras (p21(ras)) interacts directly with the catalytic subunit of phosph atidylinositol-3-OH kinase in a GTP-dependent manner through the Ras e ffector site. In vivo, dominant negative Ras mutant N17 inhibits growt h factor induced production of 3' phosphorylated phosphoinositides in PC12 cells, and transfection of Ras, but not Raf, into COS cells resul ts in a large elevation in the level of these lipids. Therefore Ras ca n probably regulate phosphatidylinositol-3-OH kinase, providing a poin t of divergence in signalling pathways downstream of Ras.