Lipid modifications of G proteins: alpha subunits are palmitoylated.
A small number of membrane-associated proteins are reversibly and covalently modified with palmitic acid. Palmitoylation of G-protein alpha and beta subunits was assessed by metabolic labeling of subunits expressed in simian COS cells or insect Sf9 cells. The fatty acid was incorporated into all of the alpha subunits examined (alpha s, alpha o, alpha i1, alpha i2, alpha i3, alpha z, and alpha q), including those that are also myristoylated (alpha o, alpha i, and alpha z). Palmitate was released by treatment with base, suggesting attachment to the protein through a thioester or ester bond. Limited tryptic digestion of activated alpha o and alpha s resulted in release of the amino-terminal portions of the proteins and radioactive palmitate. These data are consistent with palmitoylation of the proteins near their amino termini, most likely on Cys-3. Reversible acylation of G-protein alpha subunits may provide an additional mechanism for regulation of signal transduction.
Linder
M E
ME
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235.
Middleton
P
P
Hepler
J R
JR
Taussig
R
R
Gilman
A G
AG
Mumby
S M
SM
D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D003600:Cytosol / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D046911:Macromolecular Substances; D008715:Methionine / Q000378:metabolism; D008969:Molecular Sequence Data; D009036:Moths; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism*; D010957:Plasmids; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection; D014316:Tritium
D046911:Macromolecular Substances; D009227:Myristic Acids; D009838:Oligodeoxyribonucleotides; D010169:Palmitic Acids; D011994:Recombinant Proteins; D019814:Myristic Acid; D014316:Tritium; D019308:Palmitic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008715:Methionine; D019204:GTP-Binding Proteins