Palmitoylation alters protein activity: blockade of G(o) stimulation by GAP‐43

• Published in: The EMBO journal 1992-06, Vol.11 (6), p.2095-2102
• Main Authors: Sudo, Y., Valenzuela, D., Beck‐Sickinger, A.G., Fishman, M.C., Strittmatter, S.M.
• Format: Article
• Language: English
• Subjects: Animals; Brain - metabolism; Cattle; GAP-43 Protein; GTP-Binding Proteins - antagonists & inhibitors; GTP-Binding Proteins - isolation & purification; GTP-Binding Proteins - metabolism; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Kinetics; Membrane Glycoproteins - isolation & purification; Membrane Glycoproteins - metabolism; Nerve Tissue Proteins - isolation & purification; Nerve Tissue Proteins - metabolism; Palmitic Acid; Palmitic Acids - metabolism; Peptide Fragments - metabolism; Phosphoproteins - metabolism; Protein Binding
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/j.1460-2075.1992.tb05268.x

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.