G Protein γ Subunits Contain a 20-Carbon Isoprenoid

• Published in: Proceedings of the National Academy of Sciences - PNAS 1990-08, Vol.87 (15), p.5873-5877
• Main Authors: Mumby, Susanne M., Casey, Patrick J., Gilman, Alfred G., Gutowski, Stephen, Sternweis, Paul C.
• Format: Article
• Language: English
• Subjects: 550201 - Biochemistry- Tracer Techniques; Adrenal Gland Neoplasms; AMINES; Amino acids; Analytical, structural and metabolic biochemistry; ANIMAL CELLS; ANIMALS; AROMATICS; AZAARENES; BASIC BIOLOGICAL SCIENCES; Binding and carrier proteins; Biological and medical sciences; Brain Chemistry; Cattle; CELL CONSTITUENTS; Cell Line; CELL MEMBRANES; CHROMATOGRAPHY; Chromatography, Affinity; Chromatography, High Pressure Liquid; Diterpenes - analysis; ELECTROPHORESIS; Elution; ESTERS; Fundamental and applied biological sciences. Psychology; Gels; GTP-Binding Proteins - isolation & purification; GUANINE; HETEROCYCLIC COMPOUNDS; HYDROGEN COMPOUNDS; HYDROXY COMPOUNDS; Iodides; LACTONES; LIQUID COLUMN CHROMATOGRAPHY; Macromolecular Substances; MAMMALS; MEMBRANE PROTEINS; MEMBRANES; Mevalonic Acid - analogs & derivatives; Mevalonic Acid - isolation & purification; MOLECULAR STRUCTURE; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; Pheochromocytoma; PROTEINS; PURINES; Radioactive decay; RATS; RODENTS; SEPARATION PROCESSES; Terpenoids; TRITIUM COMPOUNDS; TUMOR CELLS; UPTAKE; VERTEBRATES
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.15.5873

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 α and γ 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 β and γ subunits were isolated by specific association with an affinity column of immobilized α subunits. The γ 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 α or β subunits. Isoprenylation of γ subunits by the geranylgeranyl group is presumed to contribute to the association of G proteins with membranes.