In the last 10 years we have come to appreciate the central role that phosp
hatidylinositol (PI)-4,5-P-3 plays in regulating a vast array of biological
responses to extracellular signals. The level of this phospholipid is low
in resting cells but increases rapidly in response to growth factor/cytokin
e-stimulated plasma membrane recruitment and activation of PI-3-kinase. Wit
hin the last 3 years three enzymes, SHIP: SHIP2 and PTEN, that play hey rol
es in regulating the level of PI-3,4,5-P3 have been cloned. In this review
I have attempted to summarize our current knowledge regarding these three i
ntriguing phosphatases.