Phosphatidylinositol-3 kinases functions

Helliwell, S.B. Wagner, P. Kunz, J. Deuter-Reinhard, M. Henriquez, R. Hall, M.N. TORI and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast. Mol. Biol. Cell, 5, 105-118 (1994)... 

Btk (Bruton s tyrosine kinase) is a phosphatidylinositol 3 -kinase sensitive cytoplasmic tyrosine kinase. Germline loss of function mutations of Btk cause X-linked agammaglobulinaemia in human and X-linked immunodeficiency in mice. 

Number of papers to date have shown that the CXCR4 receptors expressed in both neuronal and glial cells are functional and coupled to multiple intracellular pathways (Lazarini et al. 2003). The CXCR4 through pertussis toxin (PTX)- sensitive G proteins is coupled to at least two distinct signaling pathways (1) the first pathway, involving the activation of phosphatidylinositol- 3 (PI-3) kinase and extracellular signal... 

Figure 6.10. Phosphatidylinositol 3-hydroxy kinase activity. The enzyme phosphatidylinositol 3-hydroxy (Ptdlns 3-OH) kinase may phosphorylate inositol lipids as shown, to generate a series of novel polar lipids that may function in cell activation. See text for details.

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. 

Cooke, F.T. Dove, S.K. McEwen, R.K. Painter, G. Holmes, A.B. Hall, M.N. Michell, R.H. Parker, P.J. The stress-activated phosphatidylinositol 3-phosphate 5-kinase Fablp is essential for vacuole function in S. cerevisiae. Curr. Biol., 8, 1219-1222 (1998)... 

---