CDNA CLONING AND EXPRESSION OF THE PEPTIDE-BINDING BETA-SUBUNIT OF RAT P21RAS FARNESYLTRANSFERASE, THE COUNTERPART OF YEAST DPR1/RAM1

Protein farnesyltransferase is a heterodimeric enzyme that attaches a farnesyl group to cysteine in ras proteins and other membrane-associated proteins. The beta-subunit contains the recognition site for the peptide substrates, but is inactive in the absence of the alpha-subunit. A cloned cDNA for the rat beta-subunit predicts a protein of 437 amino acids whose mRNA is present in many tissues. Transfection of the beta-subunit cDNA produced farnesyltransferase activity in human kidney cells, but only when it was transfected together with a cDNA encoding part of the alpha-subunit. Each of the subunits appeared to be unstable in the transfected cells unless the other subunit was present. The rat beta-subunit shows 37% sequence identity with the protein encoded by the yeast DPR1/RAM1 gene, indicating that DPR1/RAM1 is the yeast counterpart of the peptide-binding subunit of the mammalian farnesyltransferase.