PHEROMONE ACTION REGULATES G-PROTEIN ALPHA-SUBUNIT MYRISTOYLATION IN THE YEAST SACCHAROMYCES-CEREVISIAE

Myristic acid (C14:0) is added to the N-terminal glycine residue of th e alpha subunits of certain receptor-coupled guanine nucleotide-bindin g regulatory proteins (G proteins). The Galpha subunit (GPA1 gene prod uct) coupled to yeast pheromone receptors exists as a pool of both myr istoylated and unmyristoylated species. After treatment of MATa cells with alpha factor, the myristoylated form of Gpa1p increases dramatica lly, and the unmyristoylated form decreases concomitantly. This pherom one-stimulated shift depends on the function of STE2 (alpha-factor rec eptor), STE11 (a protein kinase in the response pathway), and NMT1 (my ristoyl-CoA:protein N-myristoyltransferase) genes and uses the existin g pool of fatty acids (is not blocked by cerulenin). Myristoylated Gpa 1p persists long after pheromone is removed. Because myristoylation is essential for proper Galpha-Gbetagamma association and receptor coupl ing, pheromone-dependent stimulation of Gpa1p myristoylation may be an important contributing factor in adaptation after signal transmission .