FARNESYLCYSTEINE METHYLTRANSFERASE ACTIVITY AND RAS PROTEIN EXPRESSION IN HUMAN STOMACH TUMOR-TISSUE

The processing pathway of G-proteins and Ras family proteins includes the isoprenylation of the cysteine residue, followed by proteolysis of three terminal residues and alpha-carboxyl methyl esterification of t he cysteine residue. Farnesylcysteine methyltransferase (FCMT) activit y is responsible for the methylation reaction which play a role in the membrane attachment of a variety of cellular proteins. Four kinds of Ras protein (c-Ha-ras, c-N-Ras, c-Ki-Ras, pan-Ras) expression were det ected in adenocarcinoma of human tissue by immunohistochemical method, and hematoxylin and eosin staining. The level of Ras protein in human stomach tumor tissues was much higher than in normal and peritumoral regions of the same biopsy samples. The FCMT activities of each cellul ar fractions were high in mitochondrial fraction followed by microsoma l fraction, whole homogenate and cytosolic fraction. The inhibitory ef fect on FCMT activity on stomach tumor tissue was determined after tre atment with 0.25 mu M of S-adenosyl-L-homocysteine. S-adenosyl-L-homoc ysteine inhibited FCMT activity from 11.2% to 30.5%. These results sug gested that FCMT might be involved in Ras proteins activity.