Why do phosphatidylinositol kinases have so many isoforms?

Macromolecules can be transported into the cells by endocytosis, either by phagocytosis or by pinocytosis. Typically, phagocytosis involves the uptake of solid large particles mediated by cell-surface receptors, whereas pinocytosis takes up fluid and solutes. The synthesis of PtdIns(4,5)P2 and PtdIns(3,4,5)P3 plays fundamental roles in all forms of endocytosis. Curiously, almost all eukaryotic cells have multiple isoforms of the kinases that synthesize these critical phosphatidylinositols. In this issue of the Biochemical Journal, Namiko Tamura, Osamu Hazeki and co-workers report that the subunit p110alpha of the type I PI3K (phosphoinositide 3-kinase) is implicated in the phagocytosis and the pinocytosis of large molecules, whereas the receptor-mediated pinocytosis and micropinocytosis of small molecules do not seem to be controlled by this mechanism. The present commentary discusses recent literature that has begun to unravel why cells need so many phosphatidylinositol kinase isoforms, which were previously believed to be redundant.