Figure 2.

The phosphoinositide cycle as originally perceived (A) and the updated version also showing the polyphosphoinositides, PtdIns4P and PtdIns(4,5)P₂ (B). The primary event in triggering the cycle is the agonist-induced PLC activation. Note that all of the products of PtdIns(4,5)P₂ hydrolysis are recycled. Diacylglycerol (DG) is converted to phosphatidic acid (PtdOH) by one of many DG-kinase enzymes (DGK). PtdOH then has to be transferred from the PM to the endoplasmic reticulum by a mechanism that has not been identified. In the ER, one of two CDP-DG synthase (CDS) enzymes conjugates PtdOH with CTP, and the CDP-DG is then conjugated with myo-inositol to phosphatdylinositol (PtdIns). PtdIns synthesis takes place mainly in a highly dynamic subcompartment of the ER. Much of the inositol used for PtdIns synthesis is derived from the sequential dephosphorylation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P₃], the other product of PLC-mediated PtdIns(4,5)P₂ hydrolysis. Several of the dephosphorylation steps are inhibited by Li⁺, including the final dephosphorylation of inositol monophosphates by the enzyme inositol monophosphatase (IMP). The newly synthesized PtdIns has to reach the PM by a still obscure mechanism, perhaps mediated by PtdIns/PtdCho transfer proteins (PITPs).