Phosphorylation of Phospholipase A2 in Cell Proliferation

Rebecca Bowers-Gentry

Appointment Period: 2003-2004 / Grant Year: [19]

Phospholipase A2 (cPLA2) is a cytosolic enzyme responsible for the release of arachidonic acid from the phospholipids membrane of cells. The expression of cPLA2 is increased in such cancers as colorectal, small bowel, and lung cancer. It has also been reported that secreted PLA2 exerts an oncogenic activity in prostate cancer. There has been extensive research on the phosphorylation states of cPLA2 and it has been shown to be phosphorylated on various serine residues by a number of kinases, specifically mitogen-activated protein kinases (MAPKs). Furthermore, PLA2 phosphorylation has been shown to occur in response to mitogen stimulation of receptor tyrosine kinase pathways. Because MAPKs are known to regulate cellular growth and proliferation and their inhibition has been targeted in the treatment of cancer, there is a direct connection between the phosphorylation state of cPLA2 and cancer. In addition, lipids produced from the action of cPLA2 are present at tumor sites and are increased in cancers such as colon and lung cancer. For these reasons, it is clear there is a correlation between the phosphorylation of cPLA2 and cancer disease states. A major goal of my project is to identify the phosphorylation states of cPLA2 in an endogenous system to assist in determining the role that cPLA2 has in biological processes.

PUBLICATIONS (resulting from this training)

Raetz C.R., Garrett T.A., Reynolds C.M., Shaw W.A., Moore J.D., Smith D.C. Jr, Ribeiro A.A., Murphy R.C., Ulevitch R.J., Fearns C., Reichart D., Glass C.K., Benner C., Subramaniam S., Harkewicz R., Bowers-Gentry R.C., Buczynski M.W., Cooper J.A., Deems R.A., Dennis E.A. (2006). Kdo2-Lipid A of Escherichia coli, a defined endotoxin that activates macrophages via TLR-4. J Lipid Res. 47:1097-111.

Buczynski M.W., Stephens D.L., Bowers-Gentry R.C., Grkovich A., Deems R.A., Dennis E.A. (2007). TLR-4 and sustained calcium agonists synergistically produce eicosanoids independant of protein synthesis in RAW264.7 cells. J Biol Chem. May 29; [Epub ahead of print]

Murphy R.C., Bowers R.C., Dickinson J.S., Zemski Berry K.A. (2007) "Perspective on the biosynthesis and Metabolism of Eicosanoids" (P. Curtis Pryor, ed.) John Wiley & Sons, London, in press.

Bowers R.C., Cool C., Murphy R.C., Tuder R.M., Hopken M.W., Flores S.C., Voelkel N.F. (2007) Oxidative stress in severe pulmonary hypertension. Am. J. Respir. Crit. Care. Med., in review.