Chemical inhibition of myristoylation of the G-protein G(i1)alpha by 2-hydroxymyristate does not interfere with its palmitoylation or membrane association - Evidence that palmitoylation, but not myristoylation, regulates membrane attachment

The alpha-subunit of the G-protein G(il)alpha is normally dually acylated at its N-terminus with the saturated fatty acids myristate and palmitate, Inhibition of protein myristoylation by treatment with 2-hydroxymyristate prevented neither the incorporation of [H-3]palmitate nor the membrane association of this protein when expressed in COS cells. Construction of a mutant of G(il)alpha in which serine-6 was replaced by aspartic acid prevented both myristoylation and palmitoylation, and the expressed protein was found primarily in the cytoplasmic fraction. These data indicate that myristoylation is not an absolute requirement for palmitoylation of G(il)alpha and that palmitoylation, but not myristoylation, plays a key role in membrane association of this G-protein alpha-subunit.