Fibronectin-induced protein carboxy-O-methylation in aortic endothelial cells.

In a previous report (Bowersox, J.C. and Sorgente, N. (1982) Cancer Res. 42, 2547-2551) we demonstrated that the glycoprotein fibronectin is a chemoattractant for vascular endothelial cells. In probing the mechanisms by which fibronectin induces endothelial cell chemotaxis, we have discovered that the carboxy-O-methylation of cellular proteins is stimulated by fibronectin. By measuring the incorporation of L-[methyl-3H]methionine into alkali-labile, [3H]methyl ester linkages, we determined that fibronectin stimulated protein carboxy-O-methylation in aortic endothelial cells in a time- and concentration-dependent manner; the greatest stimulation occurred at 100 micrograms/ml fibronectin (approx. 35% above controls). When inhibitors of carboxymethylation were added, fibronectin-induced stimulation of protein methylation did not occur. Furthermore, inhibitors of methylation prevented the chemotaxis of endothelial cells in response to fibronectin. These data support our hypothesis that fibronectin mediates endothelial cell chemotaxis, such as that occurring during neovascularization. As carboxy-O-methylation of cell proteins is also effected by fibronectin, transmethylation reactions may be an important component of endothelial cell chemotaxis.