Signalling through phosphoinositide 3-kinases: the lipids take centre stage

Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids at the 3' position of the inositol ring to generate the 3-phosphoinositides PI(3)P, P I(3,4)P-2 and PI(3,4,5)P-3. Recent research has shown that one way in which these lipids function in signal transduction and membrane trafficking is b y interacting with 3-phosphoinositide-binding modules in a broad variety of proteins. Specifically, certain FYVE domains bind PI(3)P whereas certain p leckstrin homology domains bind PI(3,4)P-2 and/or PI(3,4,5)P-3. Also in 199 8, PTEN - a major tumour suppressor in human cancer - was also shown to ant agonise PI3K signalling by removing the 3-phosphate from 3-phosphoinositide s.