G-protein alpha-subunit expression, myristoylation, and membrane association in COS cells.

Abstract
Myristoylation of seven different .alpha. subunits of guanine nucleotide-binding regulatory proteins (G proteins) was examined by expressing these proteins in monkey kidney COS cells. Metabolic labeling studies of cells transfected with cytomegalovirus-based expression vectors indicated that [3H]myristate was incorporated into .alpha.i1, .alpha.i2, .alpha.i3, .alpha.0, .alpha.t, and .alpha.z but not .alpha.s subunits. The role of myristoylation in the association of .alpha. subunits with membranes was analyzed by site-directed mutagenesis and by substitution of myristate with a less hydrophobic analog, 10-(propoxy)decanoate (11-oxamyristate). Myristoylation of .alpha.0 was blocked when an alanine residue was substituted for its amino-terminal glycine, as was association of the protein with membranes. Substitution of the myristoyl group with 11-oxamyristate affected the cellular distribution of a subset of acylated .alpha. subunits. The results are consistent with a model wherein the hydrophobic interaction of myristate with the bilayer permits continued association of the protein with the plasma membrane when G-protein .alpha. subunits dissociate from .beta..gamma.