Abstract
Phospholipids represent a complex and structurally diverse class of molecules serving multiple critical functions within cells. In addition to serving as structural components of membranes, phospholipids act as reservoirs for the generation of bioactive lipids which function in signal transduction pathways regulating cell behavior including cell growth, differentiation, and apoptosis1. Understanding of these pathways has increased dramatically over the last 10 years in spite of the rapid interconversion of bioactive lipids and extensive crosstalk among multiple signalling pathways. Bioactive lipids bind to and regulate critical elements of the signal transduction pathways, eg. DAG/protein kinase C. Our studies demonstrate that phosphatidic acid binds in the carboxy terminus region of the protooncogene Raf-1 kinase suggesting that the generation of PA may influence the association of Raf-1 with the membrane and thus activation of the enzyme2. This is in concordance with previous studies which have shown that many of the same agonists which stimulate PC-specific phospholipase D lead to Raf-1 kinase activation. Addtionally, these results are in agreement with the observation that PA stimulates mitogenesis.
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Strum, J.C., Ghosh, S., Bell, R.M. (1997). Lipid Second Messengers. In: Honn, K.V., Marnett, L.J., Nigam, S., Jones, R.L., Wong, P.YK. (eds) Eicosanoids and other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 3. Advances in Experimental Medicine and Biology, vol 407. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1813-0_63
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