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Research Activities
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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. |
| 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.
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