Phosphoinositides phosphoinositide cleavage

Figure 14,12 Phosphoinositide cascade. The cleavage of phosphatidyl inositol 4,5-bisphosphate (PIP ) into diacyiglycerol (DAG) and inositol 1,4,5-trisphosphate (IP5) results in the release of calcium ions (due to the opening of the IP3 receptor ion channels) and the activation of protein kinase C (due to the binding of protein kinase C to free DAG in the membrane). Calcium ions bind to protein kinase C and help facilitate its activation.

Figure 1. Structure of phosphatidylinositol. Phosphatidylinositol (Ptdins) constitutes about 10% of the total phospholipids in eukaryotic cells and is the precursor of the other phosphoinositides (polyphosphoinositides) through sequential phosphorylations by specific kinases. As indicated, its inositol head group can be phosphorylated at three positions (D-3, D-4 and D-5) by specific kinases in vivo. The cleavage by phosphoinositide-specific phospholipase C (PLC), which has as its preferred substrate PtdIns(4,5)P2, is also shown. PI3K, phosphoinositide 3-kinase. PI-K II and III, phosphatidylinositol kinase types II and III. PIP-K I, phosphatidylinositol monophosphate kinase type I. PIP-K II, phosphatidylinositol monophosphate kinase type II.

Figure 2. The so-called canonical phosphoinositide pathway . The continuous phosphorylation/dephosphorylation reactions allow a steady-state level of Ptdins, PtdIns(4)P and PtdIns(4,5)P2 in the plasma membrane (PM). Cleavage of PtdIns(4,5)P2 by phospholipase C (PLC) generates the two well-known second messengers, inositol 1,4,5-trisphosphate (Ins(l,4,5)P3) and diacylglycerol (DAG). Besides its role as a protein kinase C (PKC) activator, DAG can be phosphorylated to phosphatidic acid (PA). The resynthesis of Ptdins from inositol and PA occurs mainly in the endoplasmic reticulum (ER). PPi, inorganic phosphate. PA-Pase, phosphatidic acid phosphatase. PA-TP, phosphatidic acid transport protein. PtdIns-TP, phosphatidylinositol transport protein. CDP-DAG, cytidine diphosphate-diacylglycerol. CMP, CDP and CTP, cytidine mono-, di- and triphosphate, respectively.

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