Isoprenoid addition to Ras protein is the critical modification for its membrane association and transforming activity.

• DOI: 10.1073/pnas.89.14.6403
• Publication Date: 2006-05-31T12:05:05Z
• Authors: K Kato; A D Cox; M M Hisaka; S M Graham; J E Buss; C J Der
• Keywords: Proteolysis

We have introduced a variety of amino acid substitutions into carboxyl-terminal CA1A2X sequence (C = cysteine; A aliphatic; X any acid) the oncogenic [Val12]Ki-Ras4B protein to identify acids that permit Ras processing (isoprenylation, proteolysis, and carboxyl methylation), membrane association, transformation in cultured mammalian cells. While all were tolerated at A1 position, A2 reduced transforming activity. The residue was important for both isoprenylation AAX whereas dictated extent specificity isoprenoid modification only. Differences observed between living cells farnesylation efficiency cell-free system. Finally, one farnesylated mutant did not undergo either proteolysis or methylation but still displayed efficient association (approximately 50%) activity, indicating alone can support Since are critical yeast a-factor biological three CAAX-signaled modifications may different contributions function CAAX-containing proteins.