Phosphoinositides reticulum

Scheme 1. The hydrolysis and resynthesis of phosphoinositides. Hydrolysis of phosphat-idylinositol (PI), phosphatidylinositol 4-phosphate (PIP), or phosphatidylinositol 4,5-bisphosphate (PIP2) is catalyzed by PLC in the plasma membrane. The resynthesis of phosphoinositides proceeds in the endoplasmic reticulum...

Thrombin will be used as an example of an activator of a seven transmembrane domain receptor. Uptm activation of the receptor, the Gi irotein splits into G and Gp, which both can activate PLCp (Exton, 1994 Brass et al, 1997). Q leads to phosphoinositide hydrolysis and formation of DAG and IP, which activates PKC and en ty C -stores in the endoplasmatic reticulum, respectively. The rise in [Ca causes tyrosine phosfdioi aticHi of the related acbesion focal tyrosine kinase (RAITK.) by an unidentified tyrosine kinase (TK) (Raja et al, 1997). RAFTK can also be tyrosine phosphoiylated by an unknown tyiosiiie kinase (TK.) and activated when PKC is stimulated by phoibol esters... 

Phimg, T. L., Roncone, A., Jensen, K., Sparks, C., and Sparks, J. D. (1997). Phosphoinositide 3-kinase activity is necessary for insulin-dependent inhibition of apolipoprotein B secretion by rat hepatocytes and localizes to the endoplasmic reticulum. J. Biol. Chem. 272, 30693-30702. 

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.

We have recently shown [1] that phosphatidylinositol (PI) was synthesized mainly (or perhaps exclusively) in the endoplasmic reticulum and subsequently transferred to the plasma membrane of cells to allow the phosphoinositide cycle of signal transduction to proceed we have also shown that there is nearly the same quantitative distributions of PI molecular species in plasma membranes on one side and microsomes on the other side. In both membrane preparations [2, 3] the molecular species 16 0/18 2 was largely predominant (75-80 mol%). All other molecular species (16 0/18 3,18 2/18 2,18 1/18 2, 16 0/18 1, 18 0/18 2) presented percentages lower than 8%. However the question remained do the Pl-lanase and phosphatidylinositolphosphate (Plp)-kinase, which initiate the phosphoinositide cycle in plasma membranes, discriminate between the PI molecular species ... 

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