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

Susanne M. Mumby, Robert O. Heukeroth, Jeffrey I. Gordon, Alfred G. Gilman

Research output: Contribution to journalArticle

207 Scopus citations

Abstract

Myristoylation of seven different a 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 αi2, αi2, αi3, α0, αt, and αz, but not αs subunits. The role of myristoylation in the association of α 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 α0 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 a 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 α subunits dissociate from βγ.

Original languageEnglish (US)
Pages (from-to)728-732
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number2
DOIs
StatePublished - 1990

Keywords

  • Fatty acid analog
  • Protein N-myristoylation

ASJC Scopus subject areas

  • General

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