p21ras is modified by a farnesyl isoprenoid.
Association of oncogenic ras proteins with cellular membranes appears to be a crucial step in transformation, ras is synthesized as a cytosolic precursor, which is processed to a mature form that localizes to the plasma membrane. This processing involves, in part, a conserved sequence, Cys-Ali-Ali-Xaa (in which Ali is an amino acid with an aliphatic side chain and Xaa is any amino acid), at the COOH terminus of ras proteins. Yeast a-factor mating hormone precursor also possesses a COOH-terminal Cys-Ali-Ali-Xaa sequence. However, while the COOH-terminal cysteine has been implicated as a site of palmitoylation of ras proteins, in mature a-type mating factor this residue is modified by an isoprenoid, a farnesyl moiety. We asked whether the Cys-Ali-Ali-Xaa sequence signaled different modifications for the yeast peptides (farnesylation) than for ras proteins (palmitoylation) or whether ras proteins were similar to the mating factors and contained a previously undiscovered isoprenoid. We report here that the processing of ras proteins involves addition of a farnesyl moiety, apparently at the COOH-terminal cysteine analogous to the cysteine modified in the yeast peptides, and that farnesylation may be important for membrane association and transforming activity of ras proteins.
Casey
P J
PJ
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235.
Solski
P A
PA
Der
C J
CJ
Buss
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D005204:Farnesol / Q000378:metabolism*; D011905:Genes, ras; D008798:Mevalonic Acid / Q000378:metabolism* / Q000031:analogs & derivatives; D051379:Mice; D008969:Molecular Sequence Data; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014162:Transfection
D005204:Farnesol; C015367:mevalonolactone; D015689:Oncogene Protein p21(ras); D008798:Mevalonic Acid