Phosphatidylinositol Kinase Activity in Ovarian Cancer Cells

Phosphoinositides constitute less than 0.1% of total cellular lipids, yet accumulating evidence suggests that phosphoinositide has functions in cellular growth and proliferation in addition to a role as a second messenger precursor (1,2 ). Phosphatidylinositol (PtdIns) kinases catalyze an early step in polyphosphoinositide synthesis by step-wise phosphorylation from PtdIns. Binding of certain hormones and growth factors to their specific receptors results in the increase in both polyphosphoinositides that contain phosphate at the 3-position of the inositol ring (3 ) and 4-phosphorylated phosphoinositides (4 ) (see Fig. 1). The phosphoinositide cycle that produces intracellular second messengers begins with the phosphorylation of PtdIns to form PtdIns 4-phosphate (PtdIns 4-P ) (4 ,5 ), whereas stimulation of the PtdIns kinase introducing phosphate into the 3-position appears to be associated with mitogenic responses (6 ,7 ). The PtdIns 3- and 4-kinase activities might, thereby, be important components of the mitogenic response. Although we still do not know what the physiological functions of 3-phosphorylated lipids are, there has been a considerable lifting of the mist surrounding them recently.