A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21ras to the plasma membrane.
The C-terminal CAAX motif of ras proteins undergoes a triplet of posttranslational modifications that are required for membrane association. The CAAX motif lies immediately C-terminal to the hypervariable domain, a region of 20 amino acids that distinguishes the ras proteins from each other. The hypervariable domains of p21H-ras, p21N-ras, and p21K-ras(A) contain sites for palmitoylation, which we now show must combine with the CAAX motif to target specific plasma membrane localization. Within the hypervariable domain of p21K-ras(B), which is not palmitoylated, we have identified a novel plasma membrane targeting signal consisting of a polybasic domain that also acts in combination with the CAAX motif. One function of the hypervariable domains of p21ras is therefore to provide different signals for plasma membrane localization.
Department of Haematology, Royal Free Hospital School of Medicine, London, England.
J F
JF
Hancock
H
H
Paterson
C J
CJ
Marshall
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D008715:Methionine / Q000378:metabolism; D051379:Mice; D009154:Mutation; D010169:Palmitic Acids / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D010169:Palmitic Acids; D008715:Methionine; D016283:Proto-Oncogene Proteins p21(ras)