Lipid Second Messengers and Phospholipases
Numerous signal transduction processes involve lipids as signaling molecules. Many of these molecules are generated by phospholipases such as phospholipase A2 (PLA2) which releases fatty acids such as arachidonic acid and lysophospholipids. Each of these products is implicated in signal transduction processes itself, but also serves as a precursor for eicosanoids including the prostaglandins, leukotrienes, and lipoxins or platelet activating factor (PAF). These compounds are implicated in numerous inflammatory diseases such as rheumatoid arthritis, sepsis, intestinal bowel disease (IBD), asthma as well as playing a role in cancer, atherosclerosis and premature parturition.
Numerous signal transduction processes involve lipids as signaling molecules. Many of these molecules are generated by phospholipases such as phospholipase A2 (PLA2) which releases fatty acids such as arachidonic acid and lysophospholipids. Each of these products is implicated in signal transduction processes itself, but also serves as a precursor for eicosanoids including the prostaglandins, leukotrienes, and lipoxins or platelet activating factor (PAF). These compounds are implicated in numerous inflammatory diseases such as rheumatoid arthritis, sepsis, intestinal bowel disease (IBD), asthma as well as playing a role in cancer, atherosclerosis and premature parturition.
Other important phospholipases include phospholipase C which controls the production of inositol-1,4,5-trisphosphate (IP3) which induces cytosolic Ca2+ release and diacylglycerol (DAG) which activates protein kinase C. Phospholipase D generates phosphatidic acid (PA) which subsequently can be either metabolized by PLA2 generating lysophosphophatidic acid (Lyso PA), a potent cellular mitogen, or by phosphatidate phosphohydrolase (PAP) yielding DAG. Sphingomyelinase, a phospholipase C type enzyme, and related enzymes of sphingolipid metabolism are implicated in apoptosis and other signaling processes. In summary, the phospholipases generate numerous lipid products which control much of cellular signaling and our aim is to better understand their regulation.
Other important phospholipases include phospholipase C which controls the production of inositol-1,4,5-trisphosphate (IP3) which induces cytosolic Ca2+ release and diacylglycerol (DAG) which activates protein kinase C. Phospholipase D generates phosphatidic acid (PA) which subsequently can be either metabolized by PLA2 generating lysophosphophatidic acid (Lyso PA), a potent cellular mitogen, or by phosphatidate phosphohydrolase (PAP) yielding DAG. Sphingomyelinase, a phospholipase C type enzyme, and related enzymes of sphingolipid metabolism are implicated in apoptosis and other signaling processes. In summary, the phospholipases generate numerous lipid products which control much of cellular signaling and our aim is to better understand their regulation.