Nicholas Ktistakis Tel. (01223) 496323

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Signalling pathways regulated by phosphatidic acid

Signalling pathways regulate communication between and within cells; key proteins in these pathways act very broadly to maintain cells in the appropriate functional state. However, very small changes in the genes encoding these proteins can have drastic and wide-reaching problems on cellular biochemistry.

We are interested in cellular traffic and lipid signalling with special emphasis on pathways and proteins regulated by phosphatidic acid (PA). The interaction of cellular proteins with lipid membranes is an important question in biology primarily because such interactions determine the correct subcellular localisation and activity of cellular proteins and thus the overall architecture and function of cells. PA is an essential intermediate in lipid biosynthesis but can also be formed in a signal-dependent way following activation of the enzyme phospholipase D.

Enzymes of the phospholipase D (PLD) family have been studied for over 40 years, yet the signalling pathways in which they are implicated are still a matter of debate and an intense focus of investigation. PLD enzymes hydrolyse phosphatidylcholine (PC) to generate membrane-bound phosphatidic acid (PA) and soluble choline. Whereas choline formation may be important for some aspects of PLD function, it is thought that formation of PA (and its downstream metabolite diacylglycerol) constitutes the crucial contribution of the enzyme to PLD-dependent signalling pathways. My group is interested in the structure/function characteristics of the PLD enzyme, as well as in the potential cellular targets of PA, and understanding how proteins interact with particular lipids in health and disease.