IDENTIFICATION AND CHARACTERIZATION OF A NEW ONCOGENE DERIVED FROM THE REGULATORY SUBUNIT OF PHOSPHOINOSITIDE 3-KINASE

p85/p110 phosphoinositide 3-kinase (PI3K) is a heterodimer composed of a p85-regulatory and a p110-catalytic subunit, which is involved in a variety of cellular responses including cytoskeletal organization, ce ll survival and proliferation. We describe here the cloning and charac terization of p65-PI3K, a mutant of the regulatory subunit of PI3K, wh ich includes the initial 571 residues of the wild type p85 alpha-prote in linked to a region conserved in the eph tyrosine kinase receptor fa mily. We demonstrate that this mutation, obtained from a transformed c ell, unlike previously engineered mutations of the regulatory subunit, induces the constitutive activation of PI3K and contributes to cellul ar transformation. This report links the PI3K enzyme to mammalian tumo r development for the first time.