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 the cysteine residue. Farnesylcysteine methyltransferase (FCMT) activity 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 detected 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 cellular fractions were high in mitochondrial fraction followed by microsomal fraction, whole homogenate and cytosolic fraction. The inhibitory effect on FCMT activity on stomach tumor tissue was determined after treatment with 0.25 microM of S-adenosyl-L-homocysteine. S-adenosyl-L-homocysteine inhibited FCMT activity from 11.2% to 30.5%. These results suggested that FCMT might be involved in Ras proteins activity.
Han
E S
ES
Department of Pharmacy, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, Korea.
Oh
H Y
HY
Ha
K W
KW
Han
B S
BS
Hong
S M
SM
Han
J W
JW
Hong
S
S
Noh
S H
SH
Lee
H W
HW
D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011496:Protein Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012435:S-Adenosylhomocysteine / Q000494:pharmacology; D013270:Stomach / Q000201:enzymology; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D018631:ras Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism
C057785:S-farnesylcysteine; D012435:S-Adenosylhomocysteine; D011496:Protein Methyltransferases; D018631:ras Proteins; D003545:Cysteine