title: Chemical inhibition of myristoylation of the G-protein Gi1 alpha by 2-hydroxymyristate does not interfere with its palmitoylation or membrane association. Evidence that palmitoylation, but not myristoylation, regulates membrane attachment.
abstract: The alpha-subunit of the G-protein Gi1 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 [3H]palmitate nor the membrane association of this protein when expressed in the COS cells. Construction of a mutant of Gi1 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 the myristoylation is not an absolute requirement for palmitoylation of Gi1 alpha and that palmitoylation, but not myristoylation, plays a key role in membrane association of this G-protein alpha-subunit.
authors.affiliation: Dipartimento di Farmacologia, Università di Milano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Galbiati
authors.forename: F
authors.initials: F
authors.lastname: Guzzi
authors.forename: A I
authors.initials: AI
authors.lastname: Magee
authors.forename: G
authors.initials: G
authors.lastname: Milligan
authors.forename: M
authors.initials: M
authors.lastname: Parenti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009227:Myristic Acids / Q000378:metabolism* / Q000494:pharmacology; D010169:Palmitic Acids / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D009227:Myristic Acids; D010169:Palmitic Acids; C017418:alpha-hydroxymyristic acid; D019204:GTP-Binding Proteins