CLONING AND EXPRESSION OF A CDNA-ENCODING THE ALPHA SUBUNIT OF RAT P21RAS PROTEIN FARNESYLTRANSFERASE

The complete amino acid sequence of the a subunit of heterodimeric p21ras 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 a subunit purified from rat brain. When introduced into mammalian cells by transfection, the cDNA for the a subunit produced no immunodetectable protein or farnesyltransferase activity unless the cells were simultaneously transfected with a cDNA encoding beta-subunit. In light of previous evidence that alpha-subunit forms a heterodimer with at least two different beta-subunits, current data suggest a mechanism for coordinating amounts of alpha and beta-subunits. If an alpha-subunit were stable only as a complex with a beta-subunit, the number of alpha-subunits would be automatically maintained at a level just sufficient to balance all beta-subunits, thereby avoiding the potentially toxic overaccumulation of free alpha-subunits.