TY - JOUR
T1 - A single activity carboxyl methylates both farnesyl and geranylgeranyl cysteine residues
AU - Volker, Craig
AU - Lane, Pamela
AU - Kwee, Cynthia
AU - Johnson, Mark
AU - Stock, Jeff
N1 - Funding Information:
n~krro~~/~~/WbC,t hta?nek ,rIr. sH: crskowitz ror the Suc~lrorurtr~.v cerr~isiur strains. J. Backer f’or the plasmid and bacterial strain used to prcparc recombinant human p-3l si.fu~z” and ror farncsylpyrophos-phatc. and R. Coatcs Toor all-rmrrs-gcranylgcnniol. This work was supported by grants liom the National Institutcsof Hcdlth (AI-20980 to J.S.) and the Amcricdn Cancer Socic~y (MV-486 to J.S.). C.V. was supported by a rcllowship Born the National Inslilulcs of Health (GM-08309).
PY - 1991/12/16
Y1 - 1991/12/16
N2 - Members of the Ras superfamily of small GTP-binding proteins, γ-subunits of heterotrimeric G proteins and nuclear lamin B are subject to a series of post-translational modifications that produce prenylcysteine methylester groups at their carboxyl termini. The thioether-linked polyisoprenoid substituent can be either farnesyl (C15) or geranylgeranyl (C20). Small molecule prenylcysteine derivatives with either the C15 or C20 modification, such as N-acetyl-S-trans,trans-farnesyl-L-cysteine (AFC), S-trans,trans-farnesylthiopropionate (FTP), as well as the corresponding geranylgeranyl derivatives (AGGC and GGTP) are substrates for the carboxyl methyltransferase. Saccharomyces cerevisiae ste 14 mutants that lack RAS and a-factor carboxyl methyltransferase activity are also unable to methylate farnesyl and geranylgeranylcysteine derivatives. Moreover, C20-substituted cysteine analogs directly compete for carboxyl methylation with the C15-substituted cysteine analogs and vice versa. Finally, AGGC is even more effective than AFC as an inhibitor of Ras carboxyl methylation, despite the fact that Ras is methylated at a farnesylcysteine rather than a geranylgeranylcysteine residue.
AB - Members of the Ras superfamily of small GTP-binding proteins, γ-subunits of heterotrimeric G proteins and nuclear lamin B are subject to a series of post-translational modifications that produce prenylcysteine methylester groups at their carboxyl termini. The thioether-linked polyisoprenoid substituent can be either farnesyl (C15) or geranylgeranyl (C20). Small molecule prenylcysteine derivatives with either the C15 or C20 modification, such as N-acetyl-S-trans,trans-farnesyl-L-cysteine (AFC), S-trans,trans-farnesylthiopropionate (FTP), as well as the corresponding geranylgeranyl derivatives (AGGC and GGTP) are substrates for the carboxyl methyltransferase. Saccharomyces cerevisiae ste 14 mutants that lack RAS and a-factor carboxyl methyltransferase activity are also unable to methylate farnesyl and geranylgeranylcysteine derivatives. Moreover, C20-substituted cysteine analogs directly compete for carboxyl methylation with the C15-substituted cysteine analogs and vice versa. Finally, AGGC is even more effective than AFC as an inhibitor of Ras carboxyl methylation, despite the fact that Ras is methylated at a farnesylcysteine rather than a geranylgeranylcysteine residue.
KW - GTP-binding protein
KW - Membrane attachment
KW - Prenylcysteine
KW - Protein carboxyl methylation
KW - Transforming protein
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U2 - 10.1016/0014-5793(91)81415-5
DO - 10.1016/0014-5793(91)81415-5
M3 - Article
C2 - 1765152
AN - SCOPUS:0026348178
SN - 0014-5793
VL - 295
SP - 189
EP - 194
JO - FEBS Letters
JF - FEBS Letters
IS - 1-3
ER -