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PMID: 2001678 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Methylation and proteolysis are essential for efficient membrane binding of prenylated p21K-ras(B).

The EMBO journal ·Vol. 10 ·No. 3 ·1991-03-00 ·Pages 641-6

Hancock JF, Cadwallader K, Marshall CJ

Abstract

Plasma membrane targeting of p21K-ras(B) requires a CAAX motif and a polybasic domain. The CAAX box directs a triplet of post-translational modifications: farnesylation, proteolysis of the AAX amino acids and methylesterification. These modifications are closely coupled in vivo. However, in vitro translation of mRNA in rabbit reticulocyte lysates produces p21K-ras(B) proteins which are arrested in processing after farnesylation. Intracellular membranes are then required both for proteolytic removal of the AAX amino acids and methylesterification of farnesylated p21K-ras(B). Binding of p21K-ras(B) to plasma membranes in vitro can then be shown to depend critically on AAX proteolysis and methylesterification since p21K-ras(B) which is farnesylated, but not methylated, binds inefficiently to membranes.

MeSH Terms
Animals Cell Line Cell Membrane/metabolism Dogs Esters Kinetics Methionine/metabolism Methylation Mevalonic Acid/metabolism Microsomes/metabolism Mutagenesis, Site-Directed Pancreas/metabolism Protein Binding Protein Biosynthesis Protein Processing, Post-Translational Proto-Oncogene Proteins p21(ras)/genetics,metabolism RNA, Messenger/genetics Rabbits Reticulocytes/metabolism
Chemicals
Esters RNA, Messenger Methionine Proto-Oncogene Proteins p21(ras) Mevalonic Acid
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hancock J F
Department of Haematology, Royal Free Hospital School of Medicine, London, UK.
Cadwallader K
Marshall C J
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1991-03-00
Pages
641-6
Language
English
Region
England
NLM ID
8208664
PMCID
PMC452695
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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