CLONING AND CHARACTERIZATION OF A G-PROTEIN-ACTIVATED HUMAN PHOSPHOINOSITIDE-3 KINASE

Phosphoinositide-3 kinase activity is implicated in diverse cellular r esponses triggered by mammalian cell surface receptors and in the regu lation of protein sorting in yeast. Receptors with intrinsic and assoc iated tyrosine kinase activity recruit heterodimeric phosphoinositide- 3 kinases that consist of p110 catalytic subunits and p85 adaptor mole cules containing Src homology 2 (SH2) domains. A phosphoinositide-3 ki nase isotype, p110 gamma, was cloned and characterized. The p110 gamma enzyme was activated in vitro by both the alpha and beta gamma subuni ts of heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) and did not interact with p85. A potential pleckstrin homolo gy domain is located near its amino terminus. The p110 gamma isotype m ay link signaling through G protein-coupled receptors to the generatio n of phosphoinositide second messengers phosphorylated in the D-3 posi tion.