The phosphoinositide (PI) 3-kinase family.

Phosphoinositide (PI) 3-kinase was first observed in 1984 as a minor inositol lipid kinase activity associated with immunoprecipitated oncogene products (e.g. Src, Abl and polyoma mT antigen) and present in activated growth factor receptor complexes (e.g. PDGF receptor). In 1988, the enzyme associated with this activity was found to have the novel ability to phosphorylate the 3 position hydroxyl group of the inositol ring (see poster) of phosphatidylinositol (PtdIns). PI 3kinase activities have been subsequently found in all eukaryotic cell types examined (Fry, 1994; Katso et al., 2001) and are linked to an incredibly diverse set of key cellular functions, including cell growth, proliferation, motility, differentiation, survival and intracellular trafficking (Fry, 1994; Rameh and Cantley, 1999; Fry, 2001; Katso et al., 2001). The emerging links between PI 3-kinase activity and many human maladies, including allergy, inflammation, heart disease and cancer, has made them the focus of intense study, and inhibitors of these enzymes are considered potential therapeutic agents (Stein and Waterfield, 2000).