Application Notes:
The metabolism of inositol lipids is involved in the signal transduction
of many hormones, neurotransmitters and growth factors.1,2,3 In the
classical pathway, phosphatidylinositol-specific phospholipase C (PIPLC)
hydrolyzes phosphatidyl 4,5-bisphosphate (PIP2) to yield 1,2-
diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). The role
of IP3 and DAG as second messengers is well recognized. In a second,
more recently discovered pathway, the activation of phosphoinositide
3-kinase (PI3K) results in the formation of three novel phosphatidyl
(PI) lipids phosphorylated at the D3 positions of the inositol ring: PI-3-
P, PI-3,4-P2, and PI-3,4,5-P3. These D3 lipids are not known
substrates for any of the phospholipase C enzymes and function as
second messengers. PI 3-kinase activity is correlated with many
cellular processes including the regulation of cell growth, oncogenic
transformation, chemotaxis and receptor down-regulation. A recent
paper on the effect of PI-3,4-P2 on the Akt proto-oncogene product
also contains protocols for applying PIP’s to cell cultures.4 Matreya’s synthetic phosphatidylinositols and inositol phosphates
are excellent tools for investigating these second messengers, understanding the enzyme mechanisms involved in
phosphoinositide metabolism and designing therapeutic pharmacological agents.
References:
1. Bruce A. Fenderson, E. M. Eddy, Sen-Itiroh Hakomori “Glycoconjugate expression during embryogenesis and its biological significance” BioEssays Vol. 12 pp. 173, 1990
2. P.W. Majerus, “Inositol phosphate biochemistry” Annual Review of Biochemistry Vol. 61 pp. 225-250, 1992
3. Ao-Lin Hsu, et al. “Novel Function of Phosphoinositide 3-Kinase in T Cell Ca2+ Signaling: A Phosphatidylinositol 3,4,5-Trisphostphate-Mediated Ca2+ Entry Mechanism” Journal of Biological Chemistry May, Vol. 275 pp. 16242-16250, 2000
4. H. Shimamura, et al. “The PI3-kinase-Akt pathway promotes mesangial cell survival and inhibits apoptosis in vitro via NF-kappa B and Bad” Journal of American Society of Nephrology Vol. 14 pp. 1427-1434, 2003