Enhancement of phosphoinositide 3‐kinase (PI 3‐kinase) activity by membrane curvature and inositol‐phospholipid‐binding peptides

The phosphorylation of phosphatidylinositol (PtdIns) on the 3′ position of the inositol ring by phosphoinositide 3‐kinase (PI 3‐kinase) is shown to depend strongly on the curvature of liposomes containing a mixture of phosphatidylcholine (PtdCho) and PtdIns. Vesicles with an average diameter of 50 nm are phosphorylated 100 times faster than chemically identical vesicles with an average diameter greater than 300 nm. The low reactivity of large vesicles is not due to the difference in vesicle number for large and small vesicles at constant total lipid, nor to occlusion of lipid surfaces in multilammelar structures, and can be reversed by addition of low (