Prostaglandin A2 protein interactions and inhibition of cellular proliferation

Some prostaglandins inhibit cellular proliferation in a wide variety of cell types, but the mechanism of inhibition is not known. The most potent inhibitors of proliferation appear to be prostaglandins of the A and J series. These prostaglandins have been reported to form covalent bonds to cellular proteins (Narumiya, S., Ohno, K., Fukushima, M., Fujiwara, M. (1987) J. Pharm. Exp. Ther., 242, 306-311). However, the proteins have not been identified or shown to be involved in the inhibition of proliferation. Prostaglandin A2-biotin provided a sensitive method to demonstrate binding of prostaglandin A2 (PGA2) to cellular proteins of 43, 50, and 56 kilodaltons in K562 erythroleukemia cells. Similar PGA2-binding proteins were also present in mouse fibroblasts and porcine aortic endothelial cells. The PGA2-binding proteins preexist in K562 cells and were not induced by exposure to the prostaglandin. Furthermore, binding of PGA2 to these proteins correlated to the inhibition of proliferation. Therefore, one or more of the PGA2-binding proteins may be involved in the inhibition of cellular proliferation by PGA2.