A novel membrane factor stimulates guanine nucleotide exchange reaction of ras proteins.

A factor with a molecular weight of 100 kDa, which markedly enhanced the guanine nucleotide exchange reaction of ras p21 proteins, was partially purified from bovine brain tissues. The factor was predominantly associated with the plasma membrane. When the partially purified factor and excess cold GTP were added to [3H]GDP.Gly12 p21 or Val12 in the presence of 2 mM MgCl2, the nucleotide exchange rate was stimulated up to 25-fold. The stimulation of the p21-nucleotide exchange reaction by the factor was completely blocked by the Y13-259 ras-neutralizing antibody. Taken together, these results suggest that the factor may control the rate limiting GDP/GTP exchange step in recycling of p21 in ras-mediated signal transduction.