IDENTIFICATION OF 4 NOVEL HUMAN PHOSPHOINOSITIDE 3-KINASES DEFINES A MULTI-ISOFORM SUBFAMILY

Phosphoinositide (PI) 3-kinases have critical roles in diverse cellula r signalling processes and in protein trafficking. This suggests that like other intracellular signalling molecules, e.g., phospholipase C a nd protein kinase C, there might be a large family of PI 3-kinase isof orms with the individual members having discrete signalling roles. Rev erse transcription-polymerase chain reaction methods, using degenerate oligonucleotide primers against the lipid kinase consensus region, re vealed eight sequences from human cDNA containing a high degree of ide ntity to the family of PI 3-kinases. The sequences obtained included t he previously described p110 alpha, p110 beta, and p110 gamma isoforms and HsVps34. Additionally, we have identified four novel sequences wh ich are related to PI 3-kinases. Three of the novel sequences would ap pear to form a distinct sub-family of PI 3-kinases. We report the expr ession of these novel PI 3-kinases in human tissues and in cells deriv ed from normal breast. (C) 1997 Academic Press.