Phosphatidylinositol lipid

Pleckstrin homology domain (PH-domain) was first identified at the amino and carboxyl termini of a haematopoietic protein called pleckstrin. PH-domain, a protein region of approximately 120 amino acids, by binding to phosphatidylinositol lipids of the biological membranes induces the translocation of the PH-domain containing protein to membrane compartment. Various PH-domains possess specificities for phosphoinositides phosphorylated at different sites within the inositol ring. 

The role of protein kinase C in many neutrophil functions is undisputed and has been recognised for some time. For many years it was believed that the source of DAG, the activator of protein kinase C, was derived from the activity of PLC on membrane phosphatidylinositol lipids. Whilst this enzyme undoubtedly does generate some DAG (which may then activate protein kinase C), there are many reasons to indicate that this enzyme activity is insufficient to account for all the DAG generated by activated neutrophils. More recently, experimental evidence has been provided to show that a third phospholipase (PLD) is involved in neutrophil activation, and that this enzyme is probably responsible for the majority of DAG that is formed during cell stimulation. The most important substrate for PLD is phosphatidylcholine, the major phospholipid found in neutrophil plasma membranes, which accounts for over 40% of the phospholipid pool. The sn-1 position of phosphatidylcholine is either acyl linked or alkyl linked, whereas the sn-2 position is invariably acyl linked. In neutrophils, alkyl-phosphatidylcholine (1-0-alky 1-PC) represents about 40% of the phosphatidylcholine pool (and is also the substrate utilised for PAF formation), whereas the remainder is diacyl-phosphatidylcholine. Both of these types of phosphatidylcholine are substrates for PLD and PLA2. 

PDGF, platelet-derived growth factor PDGF-RTK, platelet-derived growth factor receptor tyrosine kinase PDPK, phosphatidylinositol lipid-dependent PK... 

Other interfacial chemistries are found in juxtamem-brane domains of certain proteins that show a preferential interaction with specific lipids in their head group region. Important lipids involved in these interactions include the polyphosphate phosphatidylinositol lipids, cholesterol, gangliosides, and sphingomyelin. Interfacial chemistries play a role in the formation of microdomains and can determine the effective concentration of certain amphiphilic drugs in different membranes or even in different leaflets of the same membrane. 

In T. cruzi epimastigotes, [ H]inositol and [ P]Pi are incorporated into several phosphatidylinositol lipids consisting of phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP), and phosphatidylinositol bisphosphate (PIP2), as well as their... 

The fact that phosphatidylinositol has a fatty acid composition which is very different from that of the other phospholipids of pancreas was used to test whether the newly-formed phosphatidic acid in the stimulated tissue was derived from phosphatidylinositol (Geison et al., 1976). The structure of phosphatidylinositol from other mammalian tissues has been shown to be 1-stearoyl, 2-arachidon-oyl-sn-glycero-3-phosphorylinositol (Holub Kuksis, 1971 Baker Thompson, 1972), We find that this fatty acid composition is also typical of pancreas phosphatidylinositol. Lipid-soluble products of phosphatidylinositol which retain the diacylglycerol moiety should therefore contain stearic and arachidonic acids in equal proportions. In pancreas tissue incubated with acetylcholine, there is stoichiometry between the amounts of stearic and arachidonic acids which are lost from the phosphatidylinositol fraction and the amounts which appear in the phosphatidic acid fraction. The newly-formed phosphatidic acid appears therefore to have the same fatty acid composition as the phosphatidylinositol which is broken down. It presumably contains the 1-stearoyl, 2-arachidonoyl glycerol moiety which was originally in phosphatidylinositol. I shall use the prefix (18 0,20 4) to denote lipids which contain this moiety. The (18 0,20 4)phosphatidic acid which is formed in stimulated tissue is a novel species there is very little stearic acid and arachidonic acid in the phosphatidic acid from unstimulated pancreas. 

A. K. Menon, S. Mayor R. T. Schwarz. Biosynthesis of glycosyl-phosphatidylinositol lipids in Trypanosoma brucei involvement of mannosyl-phosphoryldolichol as the mannose donor. EMBO J, 1990, 9, 4249 258. 

---