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

Proc Natl Acad Sci U S A. 1990 Jan;87(2):728-32. doi: 10.1073/pnas.87.2.728.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cell Membrane / metabolism*
  • Cytomegalovirus / genetics
  • DNA / genetics
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism
  • Genetic Vectors
  • Kinetics
  • Macromolecular Substances
  • Mutation
  • Myristic Acid
  • Myristic Acids / metabolism*
  • Plasmids
  • Protein Processing, Post-Translational*
  • Transfection*


  • Macromolecular Substances
  • Myristic Acids
  • Myristic Acid
  • DNA
  • GTP-Binding Proteins