Cloning and expression of a cDNA encoding the α subunit of rat p21(ras) protein farnesyltransferase

The complete amino acid sequence of the α subunit of heterodimeric p21(ras) protein farnesyltransferase from rat has been deduced from the sequence of a cloned cDNA. The cDNA encodes a 377-amino acid protein that migrates on NaDodSO₄/polyacrylamide gels identically to the α subunit purified from rat brain. When introduced into mammalian cells by transfection, the cDNA for the α subunit produced no immunodetectable protein or farnesyltransferase activity unless the cells were simultaneously transfected with a cDNA encoding β subunit. In light of previous evidence that α subunit forms a heterodimer with at least two different β subunits, current data suggest a mechanism for coordinating amounts of α and β subunits. If an α subunit were stable only as a complex with a β subunit, the number of α subunits would be automatically maintained at a level just sufficient to balance all β subunits, thereby avoiding the potentially toxic overaccumulation of free α subunits.