Palmitoylation alters protein activity: blockade of G(o) stimulation by GAP-43.
The addition of palmitate to cysteine residues enhances the hydrophobicity of proteins, and consequently their membrane association. Here we have investigated whether this type of fatty acylation also regulates protein-protein interactions. GAP-43 is a neuronal protein that increases guanine nucleotide exchange by heterotrimeric G proteins. Two cysteine residues near the N-terminus of GAP-43 are subject to palmitoylation, and are necessary for membrane binding as well as for G(o) activation. N-terminal peptides, which include these cysteines, stimulate G(o). Monopalmitoylation reduces, and dipalmitoylation abolishes the activity of the peptides. The activity of GAP-43 protein purified from brain also is reversibly blocked by palmitoylation. This suggests that palmitoylation controls a cycle of GAP-43 between an acylated, membrane-bound reservoir of inactive GAP-43, and a depalmitoylated, active pool of protein.
Sudo
Y
Y
Developmental Biology Laboratory, Massachusetts General Hospital, Charlestown.
Valenzuela
D
D
Beck-Sickinger
A G
AG
Fishman
M C
MC
Strittmatter
S M
SM
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D019922:GAP-43 Protein; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism*; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000378:metabolism*; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010169:Palmitic Acids; D010446:Peptide Fragments; D010750:Phosphoproteins; D019308:Palmitic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins