Posttranslational modification of the Ha-ras oncogene protein: Evidence for a third class of protein carboxyl methyltransferases

S. Clarke, J. P. Vogel, R. J. Deschenes, J. Stock

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Abstract

The ras oncogene products require membrane localization for their function, and this is thought to be accomplished by the addition of a palmitoyl group to a cysteine residue near the carboxyl terminus of the nascent chain. A lipidated carboxyl-terminal cysteine residue is also found in sequence-related yeast sex factors, and in at least two cases, the α-carboxyl group is also methyl esterified. To determine if ras proteins are themselves modified by a similar type of methylation reaction, we incubated rat embryo fibroblasts transformed with p53 and activated Ha-ras oncogenes with L-[methyl-3H]methionine under conditions in which the isotope was converted to the methyl donor S-adenosyl-L-[methyl-3H]methionine. By using an assay that detects methyl ester linkages, we found that immunoprecipitated ras proteins are in fact esterified and that the stability of these esters is consistent with a carboxyl-terminal localization. This methylation reaction may be important in regulating the interaction of ras proteins with plasma membrane components. The presence of analogous carboxyl-terminal tetrapeptide sequences in other proteins may provide a general recognition sequence for lipidation and methylation modification reactions.

Original languageEnglish (US)
Pages (from-to)4643-4647
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number13
DOIs
StatePublished - 1988

All Science Journal Classification (ASJC) codes

  • General

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