PHOSPHOINOSITIDE 3-KINASES AND MEMBRANE TRAFFIC

Phosphoinositide 3-kinases (PI 3-kinases) and their 3-phosphoinositide products were identified initially as components of intracellular sig nalling pathways emanating from cell surface receptors. A new role for 3-phosphoinositides in the constitutive movement of proteins from one intracellular compartment to another was proposed with the discovery of homology between the product of a yeast gene important for vacuolar sorting, Vps34p, and a mammalian PI 3-kinase. Recent studies have imp licated PI 3-kinase as an essential component in membrane traffic at s pecific steps of the trans-Golgi-network-endosomal-pre-lysosomal syste m. Evidence largely emerging from the insulin-stimulated glucose trans port system suggests that PI 3-kinase may also mediate the effects of growth factors on membrane traffic events. These studies suggest a pos sible link between growth-factor-stimulated and constitutive membrane traffic in the endosomal system.