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.
Hancock
J F
JF
Department of Haematology, Royal Free Hospital School of Medicine, London, England.
Paterson
H
H
Marshall
C J
CJ
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)