Abstract
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.
Original language | English (US) |
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Pages (from-to) | 189-194 |
Number of pages | 6 |
Journal | FEBS Letters |
Volume | 295 |
Issue number | 1-3 |
DOIs | |
State | Published - Dec 16 1991 |
All Science Journal Classification (ASJC) codes
- Genetics
- Molecular Biology
- Biophysics
- Structural Biology
- Biochemistry
- Cell Biology
Keywords
- GTP-binding protein
- Membrane attachment
- Prenylcysteine
- Protein carboxyl methylation
- Transforming protein