G protein gamma subunits contain a 20-carbon isoprenoid.
A small subset of cellular proteins are covalently modified by the addition of isoprenoid groups. These include p21ras, fungal mating factors, and nuclear lamins, which are isoprenylated at carboxyl-terminal cysteine residues with a 15-carbon farnesyl group. The similarity of the carboxyl-terminal sequences of these proteins with the alpha and gamma subunits of signal-transducing guanine nucleotide-binding regulatory proteins (G proteins) prompted examination of isoprenylation of G protein subunits. PC-12 cells were incubated with the isoprenoid precursor [3H]mevalonolactone. The beta and gamma subunits were isolated by specific association with an affinity column of immobilized alpha subunits. The gamma subunits were radiolabeled, and the tritiated lipid released from them by treatment with methyl iodide comigrated chromatographically with the 20-carbon isoprenoid geranylgeraniol. Label was not detected in G protein alpha or beta subunits. Isoprenylation of gamma subunits by the geranylgeranyl group is presumed to contribute to the association of G proteins with membranes.
Mumby
S M
SM
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235.
Casey
P J
PJ
Gilman
A G
AG
Gutowski
S
S
Sternweis
P C
PC
D000310:Adrenal Gland Neoplasms; D000818:Animals; D001923:Brain Chemistry; D002417:Cattle; D002460:Cell Line; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes / Q000032:analysis*; D019204:GTP-Binding Proteins / Q000302:isolation & purification*; D046911:Macromolecular Substances; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000302:isolation & purification; D010673:Pheochromocytoma; D051381:Rats
D004224:Diterpenes; D046911:Macromolecular Substances; C015367:mevalonolactone; C017338:geranylgeraniol; D019204:GTP-Binding Proteins; D008798:Mevalonic Acid