Lipid kinases are one of the most promising new classes of potential drug targets. PI-3 and sphingosine kinases regulate a wide variety of cellular functions, including cell growth, proliferation, differentiation, motility, intracellular trafficking, and survival. As a result, defects in lipid kinase function lead to multiple disease states, including several forms of cancer and diabetes.
The phosphatidylinositol 3-kinases (PI3Ks) are grouped into three classes (I – III) which differ in structure and function. Class I enzymes have been intensely studied and have emerged as promising drug targets in cancer and in immune disorders. PI3K are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. Many of these functions relate to the ability of class I PI 3-kinases to activate protein kinase B (PKB, aka Akt) as in the PI3K/AKT/mTOR pathway.
Diacylglycerol kinase (DGK or DAGK) is a family of enzymes which phosphorylates diacylglycerol (DG) resulting in the production of phosphatidic acid (PA). In non-stimulated cells, DGK activity is low allowing DAG to be used for glycerophospholipid biosynthesis but on receptor activation of the phosphoinositide pathway, DGK activity increases driving the conversion of DAG to PA. As both lipids are thought to function as bioactive lipid signaling molecules with distinct cellular targets, Diacylglycerol kinase is thought to be a key enzyme that regulates numerous cellular responses by regulating balance of the two lipid messengers.