The Journal of Biological Physics and Chemistry

Farnesylation and nitrosylation of p21Ras change its intrinsic GTPase activity

N. Narmania, E. Zhuravliova, T. Barbakadze and D. Mikeladze

Ras proteins perform functional roles in a large number of biological processes leading to changes in cell morphology, gene expression, survival and apoptosis. Ras is regulated by a series of post-translational modifications including farnesylation, and nitrosylation, but the role of these modifications in governing the activity of Ras is not fully understood. Using several chromatographic steps, soluble and membrane-bound Ras proteins from bovine brain were purified, and incubated with either S-nitrosocysteine or farnesyl transferase and farnesyl diphosphate. In the presence of S-nitrosocysteine the activity of soluble Ras was increased, whereas farnesylation caused a significant inhibition of GTPase activity. In contrast, inhibition of GTPase activity was observed after incubation of S-nitrosocysteine with membrane-derived Ras. Our results suggest that different cysteine residues were S-nitrosylated in the membrane-derived and soluble Ras-proteins and that these modifications can regulate GTPase activities.

Keywords: farnesylation, nitrosylation, p21Ras